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Retina Transplant Difficulties

Retina Transplant Difficulties


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Why is retina transplant not as easy as the normal eye donation and transplant (I think the latter involves the cornea ) ?
This says that a new method has come up but why isnt the process similar and simple as the normal transplant ?
What are the difficulties in retina transplant ?


This is a diagram of a cross-section of the cornea:

It is an amazing but relatively simple structure, the shape of which is responsible for about 60% of our focusing power, and the clarity of which allows light to enter. It is avascular (no blood vessels), and the non-mylenated nerve endings are very tiny and present in the epithelium.

Transplanting this relatively simple tissue is easy (well, not do-it-at-home easy, but easy.) The only problem with cutting all those nerve endings is that the new cornea will feel nothing if there's dust in the eye, etc. This is a problem, but nothing compared to blindness.

This is a diagram of a cross section of the retina:

As you can see, it is not nearly as simple as the cornea. The nerves (to the left: yellow, light blue, medium blue and darker blue), which collect information from the rods and cones (pink and purple) are very numerous, and absolutely vital to the ability of the brain to interpreting information from these photoreceptors. Therefore, a cut piece of retina immediately loses the ability to send any information to the brain. To transplant it into an eye with a damaged retina would do nothing to improve vision. Also, it is not easy surgery. It's very difficult.

What has been called "retinal transplants" in the recent past have been tiny pieces of embryonic retina, about…

4 millimetre square of retinal tissue, complete with retinal progenitor cells and the retinal pigment epithelium that nourishes them. The tissues were placed in the sub-retinal space beneath the fovea, the area of the retina responsible for sharp central vision.

Note, they didn't try to connect nerves or blood vessels. And, it came from an embyro (so the supply is a problem.) The improvement in vision - which was significant in 7 out of 8 recipients (one patient going from 20/800 to 20/160) - is not long lasting, and believed to have been not from the transplanted retina connecting to the existing retina, but from the release of growth factors from the embryonic tissue improving the health of the degenerating retina.

The newest in "retinal transplants" (which might be better called stem-cell-supplied growth factors implanted in the retina) actually derives from the patient's own stem cells:

A Japanese woman in her 70s is the first person to receive tissue derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same regenerative potential as embryo-derived cells but without some of the ethical and safety concerns. [No news yet on whether it worked.]

In a two-hour procedure… a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital implanted a 1.3 by 3.0 millimetre sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration, a common eye condition that can lead to blindness.

TL;DR: It's not as easy as taking cadaver retina and replacing a patients retina (that would result in immediate and permanent blindness). Whereas corneal transplantation is very easy.

Corneal Innervation and Cellular Changes after Corneal Transplantation: An In Vivo Confocal Microscopy Study
Retinal transplants see fleeting success
Japanese woman is first recipient of next-generation stem cells


Is an Eye Transplant Possible?

Scott Sundick, MD, is a board-certified vascular and endovascular surgeon. He currently practices in Westfield, New Jersey.

You may hear the words "eye transplant" used by patients, but a true eye transplant surgery is not possible. An entire eye cannot be taken from one person and transplanted into another person in order to improve vision. That does work with organ transplants and some tissues, but cannot be done with an entire eye with current medical knowledge and techniques.

Currently, the only eye transplant procedure that is available is the cornea transplant, which replaces a diseased cornea with a cornea donated by a deceased donor. A cornea transplant can produce remarkable changes in vision. In fact, some individuals can be legally blind prior to surgery and find their vision is 20/20 after a cornea transplant.  

Unlike organ transplants, individuals who receive a cornea transplant do not require anti-rejection medications to maintain their cornea transplant.


Scientists Set Sights on 1st Whole-Eye Transplant

THURSDAY, Oct. 30, 2014 (HealthDay News) -- In the world of 21st-century medicine, organ transplantation is nothing new.

The first kidney transplant took place in 1950, followed by the first liver transplant in 1963 and the first human heart transplant in 1967. By 2010, doctors had even managed the transplantation of a patient's entire face.

One major organ still eludes the transplant surgeon, however: the entire human eye. But if one team of U.S. scientists has its way, that dream may become reality, too.

"Until recently, eye transplants have been considered science fiction," said Dr. Vijay Gorantla, an associate professor of surgery in the department of plastic surgery at the University of Pittsburgh. "People said it was crazy, bonkers."

However, "with what we now know about transplantation and, more importantly, nerve regeneration, we are finally at the point where we can have real confidence that this is something that actually can be pursued and eventually achieved," he said.

Continued

Whole-eye transplants would be of enormous benefit for many of the 180 million blind or severely visually disabled people around the world, including nearly 3.5 million Americans, experts say.

"Macular degeneration and glaucoma are the root cause of much the world's visual impairment," explained Dr. Jeffrey Goldberg, director of research at the Shiley Eye Center at University of California, San Diego.

Certainly, there are therapies that often help restore sight in these cases, or in people who've lost sight through injury. "But for some people the eye is too damaged or too far gone," Goldberg said. "For patients with a devastating eye injury where there's no remaining connective optic nerve -- or perhaps not even an eyeball in their eye socket -- restorative approaches are simply not enough."

In these cases, transplantation of a healthy donor eye would be a solution. "It's a scientific long shot," Goldberg said. "But it's a very attractive long shot."

So, Gorantla and Goldberg -- and their two universities -- have teamed up to push whole-eye transplantation from theory into practice. The effort is funded by the U.S. Department of Defense.

Continued

One of the biggest challenges is how to regenerate and regrow delicate optical nerves.

"The chief problem," Goldberg explained, "is that when you switch out an eyeball you have to completely cut all connections between the optic nerve and the eye. So then you need to reconnect the donor eye's nerve fibers back to the recipient's brain in order to achieve vision restoration. But we know that once you make that cut, the nerve fibers just do not regrow on their own. That doesn't happen automatically."

"That's what distinguishes an eye transplant from most other types of transplants," Gorantla added. In other organ transplants, the chief hurdle is simply reconnecting a proper blood supply. "For example, if you get the plumbing connected and the blood going, then a transplanted heart will beat in the recipient patient immediately," Gorantla said.

"But an eye transplant actually has more parallels with a hand or face transplant," he said. The eye may appear healthy because of a renewed blood supply, but without reconnecting the optic nerve, "there's no motor activity and no sensation or eyesight," Gorantla said. "The result is functionless and lifeless."

Continued

Luckily, various laboratories "have made significant progress" in fostering the long distance regrowth of nerve fibers, Goldberg said. "In animals with optic nerve injury or degeneration we've even started to see fibers regrow all the way back to the brain," he noted.

The regeneration of cells called retinal ganglia cells -- key to achieving discernible vision -- has also met with recent success in a lab setting. "The recent indications that such nerve generation is actually possible raises optimism that eye transplantation can really be viable," said Gorantla, who is also administrative medical director of the Pittsburgh Reconstructive Transplant Program at the University of Pittsburgh Medical Center.

Still, any first attempt at a whole-eye transplant in humans remains years away, the experts cautioned.

"There's a significant amount of work to be done before anything like this can be tried on patients," Goldberg said. "But when you survey people, losing one's vision comes in just a smidge below death as a thing we fear. There are few things people value more than their vision, so while it may be audacious, it's worth the effort."


ROP occurs when abnormal blood vessels grow and spread throughout the retina, the tissue that lines the back of the eye. These abnormal blood vessels are fragile and can leak, scarring the retina and pulling it out of position. This causes a retinal detachment. Retinal detachment is the main cause of visual impairment and blindness in ROP.

Several complex factors may be responsible for the development of ROP. The eye starts to develop at about 16 weeks of pregnancy, when the blood vessels of the retina begin to form at the optic nerve in the back of the eye. The blood vessels grow gradually toward the edges of the developing retina, supplying oxygen and nutrients. During the last 12 weeks of a pregnancy, the eye develops rapidly. When a baby is born full-term, the retinal blood vessel growth is mostly complete (the retina usually finishes growing a few weeks to a month after birth). But if a baby is born prematurely, before these blood vessels have reached the edges of the retina, normal vessel growth may stop. The edges of the retina — the periphery — may not get enough oxygen and nutrients.

Scientists believe that the periphery of the retina then sends out signals to other areas of the retina for nourishment. As a result, new abnormal vessels begin to grow. These new blood vessels are fragile and weak and can bleed, leading to retinal scarring. When these scars shrink, they pull on the retina, causing it to detach from the back of the eye.


Common Health Problems After an Organ Transplant

Most people who have an organ transplant live a pretty normal life. But organ transplants can still lead to other medical problems. This is usually because of the medicines needed to suppress the immune system so it doesn't "fight" the donor organ.

These problems range from the annoying to the life-threatening. Here's a rundown of some of them.

  • Diabetes. Diabetes can be a new problem or a problem that is exacerbated after the transplant. Some transplant medications can be responsible.
  • High cholesterol.High cholesterol doesn't have any symptoms itself, but it's still dangerous. It can clog up your blood vessels, possibly damage your donor organ, and eventually lead to heart disease. It's a fairly common side effect of some of the medications used to control your immune system response after a transplant.
  • High blood pressure. Again, the medicines you need can aggravate or cause high blood pressure. While it can be a serious condition, it may get better as you taper off your medication. You may need to change some of your habits, too. Make sure to eat a healthy diet and get regular exercise.
  • Gastrointestinal problems. This is a fairly common side effect of steroids. Your health care professional may prescribe medication to help. On your own, do what you can to settle your stomach. Take medication with meals to reduce irritation. Cut down on alcohol and drinks with caffeine.
  • Gout. A buildup of uric acid in the blood can result in gout, a painful inflammation of some joints. It can be caused or worsened by some of the post-transplant medications used to suppress your immune system. Treatment depends on your specific case. It may be possible to change some of your medications to control the condition.
  • Anxiety and depression. People who have received a transplant have usually been through a lot of frightening and nerve-racking experiences: coping with a life-threatening disease, waiting for a transplant, recovering from serious surgery and readjusting to life. It's not surprising that many people develop chronic anxiety and depression. Medications can make them worse and cause mood swings. But don't ever accept these conditions as normal. Get help. Talk to your organ transplant team. There's no reason for you to suffer.
  • Sexual problems. Some people who have a transplant develop some sexual problems, such as a decreased sex drive or loss of function. These symptoms can be caused by health problems, your medication, stress, or a combination. Although it may feel embarrassing, get help. There's nothing to be ashamed of. Your health care provider may be able to resolve the problem.
  • Unwanted hair growth. The solution to this problem is the obvious: try shaving, waxing, or using drugstore products that remove hair.

Sources

National Kidney Foundation.

United Network for Organ Sharing.

United Network for Organ Sharing's "Transplant Living" web site.

Health Resources and Services Administration: "Partnering with Your Transplant Team: The Patient's Guide to Transplantation."


News and Announcements from the CDB

Improved vision in retinal degeneration mice after iPSC-derived retina transplants

The retina is a layered neural structure at the back of the eye that plays an important role in sensing and translating light information entering the eye into neural signals sent to the brain. Light is sensed by photoreceptors (rods and cones) in the outer nuclear layer, the outermost layer of the neural retina, and this information is then transmitted in turn through the bipolar cell layer, ganglion cell layer, and finally to the optic nerve that will send neural signals to the brain to be interpreted into what we “see.” Disruption to any segment of this neural transmission can affect vision. Retinitis pigmentosa is a group of genetic eye disorders characterized by progressive degeneration of retinal photoreceptors resulting in severe visual impairment, and there is currently no effective treatment to restore visual function in affected patients. Some groups have reported that transplantation of retinal tissue or stem cell-derived photoreceptors into the eye shows slight restoration of visual function, but it remained unclear whether transplanted tissues or photoreceptors actually integrated with the surrounding host environment.

A new study led by Deputy Project Leader Michiko Mandai of the Laboratory for Retinal Regeneration (Masayo Takahashi, Project Leader) has demonstrated that following transplantation of induced pluripotent stem cell (iPSC)-derived retinal tissue into end-stage retinal degeneration (rd1) model mice, the photoreceptors in the transplanted tissue can form functional synapses with synaptic partners in the host eye using cell labeling, behavioral analyses and electrophysiological recordings. Their work was published in the journal Stem Cell Reports.

A series of studies by the former CDB Laboratory for Organogenesis and Neurogenesis led by the late Yoshiki Sasai established a cell culture method for directing embryonic stem cells (ESCs) to self-organize into 3D tissue structures and also reported the successful generation of 3D-retinal tissue from mouse and later human embryonic stem cells (ESCs) (Science News: April 7, 2011 June 14, 2012). Mandai and her team expanded on this work to examine feasibility of using this stem cell-derived retinal tissue for transplantation to restore vision in retinal degenerative diseases. They reported that mouse ESC/iPSC-derived retinal tissue could mature and survive when transplanted into mouse eye (Science News: April 25, 2014), and observed similar results transplanting human ESC-derived retinal tissue in monkey models (Science News: January 29, 2016). Although the retinal grafts appeared to integrate with surrounding host retina in both studies, they could not ascertain whether the graft had fully integrated with the host to sense light and transmit neural signals.

The group first examined the synaptic connections between the photoreceptors in transplanted tissue and the surrounding host cells, specifically with bipolar cells. They generated and transplanted iPSC-derived retina expressing red fluorescent markers at the synaptic terminal ends of photoreceptors into an rd1 mouse line that expressed green fluorescent markers in dendrites of bipolar cells. They were able to visually confirm that the red photoreceptor synaptic terminal ends of their transplanted retinal tissue were in contact with green host bipolar cell dendrites.

Next, they used a behavioral learning experiment, called shuttle avoidance system (SAS), on rd1 mice to determine whether these mice could in fact detect light following transplantation of iPSC-derived retina. In SAS, mice can be trained to associate stimulus, such as light, with electrical shock and will move to avoid getting shocked when they sense light. Thus, if the iPSC-derived retina had formed functional synapses with host cells, the transplant recipient rd1 mice should be able to be trained to associate light stimulus with an electrical shock and show avoidance behavior if light is detected. Their analyses revealed that some transplant recipient rd1 mice displayed avoidance responses, while rd1 mice that did not receive transplants moved at random regardless of light stimulus.

  1. Behavioral analyses using shuttle avoidance system. rd1 mouse displaying light-responsive avoidance behavior after iPSC-derived
    retina transplant (top). rd1 mouse that did not display light-responsive avoidance behavior after iPSC-derived retina transplant (bottom).

The team also extracted the whole retina of rd1 mice post-transplantation to examine their ability to transmit electrophysiological signals using a microelectrode array (MEA) system. The extracted whole retina tissues were laid flat on microchips and analyzed for their responses to light signals. The team found that the retinal graft areas responded to light signals similar as seen in normal retina, and that graft-derived photoreceptors transmitted excitatory signals via bipolar cells to host retinal ganglion cells.

“Presently, we can only transplant tissue sizes equivalent to less than 5% of the whole retina with our method. If we can improve our technique to allow transplantation of larger tissues, this may lead to a marked improvement in vision,” says lead author Mandai. “Our study demonstrates a proof-of-concept for considering clinical transplantation of iPSC-derived retinal tissues into patients with retinal degeneration. Aside from improving transplant techniques and testing whether human iPSC-derived retina can restore vision in blind mice, we also need to assess the safety of the transplant procedure and of the derived retinal tissue itself before we can move to human clinical studies.”


Are there any side effects?

Like any surgery, corneal transplant surgery has risks. One major risk is tissue rejection, when your body sees the new cornea as a foreign object and tries to get rid of it. Your doctor can give you medicine to help stop the rejection and save your cornea.

Corneal transplant can also cause other eye problems, including:

If you have tissue rejection or other severe problems with your new cornea, you may need another transplant. Talk with your doctor about the risks of corneal transplant and whether this treatment is right for you.


Stem Cell Therapy in Retinal Disease

Stem cells, currently under investigation for the treatment of age-related macular degeneration and other retinal disorders, are characterized by the ability to differentiate into multiple cell lineages, and an unlimited self-renewal capacity. These traits make them excellent candidates as potential treatments for various diseases. To date, however, no stem cell-based therapy for retinal disease has been approved by the U.S. Food and Drug Administration, though there are several c

Figure 1. Embryonic stem cell-based therapy. The inner cell mass is isolated from the blastocyst and cultured. The pluripotent embryonic stem cells are then differentiated into retinal pigment epithelium, photoreceptor precursors or other cell types using various methods.

andidates in development. In this article, we’ll focus on human studies of stem cell-based ocular therapy.

Stem Cell Primer
Pluripotent stem cells (PSCs), by definition, are able to differentiate into all endodermal, mesodermal and ectodermal lineages. Human embryonic stem cells (hESCs) were first cultured in 1998 and have the potential to differentiate into all cell types (Figure 1) . They are a promising source for stem cell-based therapy but, like fetal progenitor cells, raise potential ethical considerations. Induced pluripotent stem cells (iPSCs) are a subtype of pluripotent stem cells that originate from a differentiated cell source, such as skin fibroblasts or blood cells (Figure 2) they may be considered less controversial, and may negate some immunological issues associated with hESC-based therapies. Somatic stem cells, such as bone marrow, adipose, central nervous system and umbilical stem cells, are different than ESC- or iPSC-based therapies because they’re not pluripotent, but can generate some of the cell types of their host organ. While they normally assume a regenerative role in their host organ (i.e., corneal limbus epithelial stem cells), somatic stem cells typically assume a trophic role in stem cell therapy (Figure 3) .

It turns out that the eye is a good candidate for stem cell clinical research, given the unmet therapeutic need, the relatively immune-privileged site and the clear ocular media that facilitates direct visualization of transplanted cells. Furthermore, the size of the eye requires smaller quantities of therapeutic tissue in comparison to other organs.

In the eye, stem cells can potentially serve two different therapeutic roles: regenerative or trophic. For example, stem cells have the potential to replace or regenerate tissue, such as retinal ganglion cells in glaucoma, or retinal pigment epithelium in retinitis pigmentosa or AMD-related geographic atrophy (GA). They can alternatively or simultaneously assume a trophic role, producing growth factors and cytokines, such as brain-derived neurotrophic factor, that have a supportive paracrine effect on local structures within the macula. (It’s worth noting that most current approaches using somatic stem cells to treat retinal disease use an intravitreal delivery method, in contrast to subretinal transplantation. 1 )

RPE Transplantation
Transplant of retinal pigment epithelium cells is a popular application of stem cell therapy in ophthalmology, with researchers taking different approaches:

• Embryonic stem cells in RPE transplantation. The first human studies of stem cell-based RPE transplants in AMD and Stargardt Disease were published in 2012. 1 Steven D. Schwartz, MD, of the Stein Eye Institute in Los Angeles, and his colleagues performed two prospective clinical trials of subretinal transplantation of hESC-derived RPE cells in nine patients with Stargardt macular dystrophy and nine with atrophic AMD. 2 Following surgery combined with immunosuppression, 72 percent of patients had increased subretinal pigmentation at the location of the transplant, suggesting the presence of the injected cells. 2 No serious adverse outcomes were observed in visual acuity, visual field, static perimetry, electroretinography or reading speed, and there were no signs of acute rejection. Even after four years, none of the eyes developed abnormal growth suggestive of a teratoma, a tumor composed of two or more germ layers which could originate from stem cells, and no eyes developed proliferative vitreoretinopathy or a retinal detachment. 2,3

In 2015, Won Kyung Song, MD, of Korea’s Bundang Medical center, and co-workers published preliminary results of subretinal hESC-derived RPE transplantation in two patients with advanced atrophic AMD and two patients with Stargardt disease. 4 Si

Figure 2. The process of inducing pluripotency followed by differentiation of cells into the desired cell type. First, a tissue is harvested from the adult patient. The tissue is then processed and the desired cell type isolated and cultured. The cells are then induced into pluripotency through the introduction of particular factors and growth conditions. Once pluripotency is established, the cells can be differentiated into the desired cell type, such as retinal pigment epithelium or photoreceptor precursor cells.

milar to Dr. Schwartz’s study, no patients developed teratomas, graft rejection, PVR or a significant visual decline. However, this study did note some challenges expected with surgery surrounding retinotomy sites, as well as intolerance of immunosuppression in one patient. 4

A recent Phase I trial of hESC transplants on a coated, synthetic basement membrane in two patients with advanced exudative AMD was suggestive of survival of the graft through 12 months. The study highlighted the feasibility of transplantation of RPE cells on the synthetic membrane, but also identified perioperative challenges, including a
retinal detachment due to PVR, dislocation of a fluocinolone implant used for immunosuppression and worsening of diabetes from the use of oral steroids. 5

• Induced pluripotent stem cells in RPE transplantation.The use of iPSC-derived RPE transplants in human trials has lagged behind the use of ESCs. The first human trial using iPSC-derived RPE subretinal transplants was initiated by RIKEN, a research institute in Kobe, Japan, in September 2014. 6 A 70-year-old Japanese woman became the first person to receive an iPSC-derived therapy for any indication. 7 She didn’t receive immunosuppression, in contrast to ESC-derived RPE transplantation studies. 2,4 The subject demonstrated no adverse ocular effects at one year, the transplanted sheets remained intact and her vision decline had stabilized. 8 This study was suspended after mutations were observed in a second subject’s iPSCs, which weren’t detectable in the patient’s original fibroblasts. 6

In 2016, RIKEN planned to resume the study, with a significant modification: Instead of autologous cells, its researchers are investigating human leukocyte antigen-matched allogenic iPSC-derived RPE cells. 6

The use of autologous cells is costly and may require up to three months to develop from harvesting to intraocular implantation. 7 In contrast, the use of allogenic cells facilitates verification of genomic stability and expedites the time from patient selection to implantation. 6

A potential downside of using allogenic cells, however, is the increased risk of rejection due to the presentation of non-self antigens and the possible need for immunosuppression.

Trophic Roles for Stem Cells
Human intravitreal, autologous bone marrow-derived mononuclear transplantation was first published in 2008, and demonstrated no significant safety issues in an eye with advanced diabetic retinopathy with optic nerve atrophy and retinal detachment. 9 The same group expanded the study to include two additional patients, including a patient with advanced atrophic AMD. Two of the three patients underwent pars plana vitrectomy followed by intravitreal transplantation of suspended cells, and the third patient had the transplant injected into silicone oil. In all patients, the cells disappeared within four weeks, and other than a mild increase in intraocular pressure (absolute readings of 15 to 30 mmHg), no adverse events were published. 10

A separate group investigated the intravitreal injection of autologous CD34+ bone marrow stem cells in various retinal pathologies. In contrast to the studies mentioned above, this group didn’t perform PPV prior to intravitreal injection. The transplant was tolerated well with no intraocular inflammation or tumor formation. At six mon

Figure 3. Somatic stem cell therapy. First, tissue is harvested from the patient and the desired cell is isolated and purified. The cells can then variably be modified and are typically injected intravitreally where they have a paracrine effect. Alternatively, the tissue can be injected subretinally and some investigators are investigating periocular injections.

ths postoperatively, five of the six study eyes demonstrated VA stabilization, but one eye developed progression of AMD-related GA with a visual decline. 11 Overall, these studies suggest the basic tolerability of the procedure, with further studies needed to clarify safety and efficacy. Other human studies have investigated the use of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa, retinal vein occlusion and cone-rod dystrophy. 12-14

Postoperatively, patients injected with mesenchymal or hematopoietic stem cell-based therapies may be at increased risk of proliferation of cells within the vitreous. For example, following intravitreal injection of CD34-positive stem cells, a 71-year-old female patient developed a visually significant epiretinal membrane within four months. 15 Another patient, a 60-year-old man with Stargardt disease, developed a retinal detachment two months following subretinal injection of autologous mesenchymal stem cells. 16 Most recently, Ajay E. Kuriyan, MD, at the University of Rochester Medical Center in Rochester, New York, published an account of a tragic case series of three patients who experienced vitreous proliferation, retinal detachment and profound loss of vision following adipose tissue-derived mesenchymal stem cell intravitreal transplants at one center in Florida. 17 One of the patients saw the treatment on www.clinicaltrials.gov, and erroneously interpreted the listing as a clinical trial with government approval and oversight, even though the center billed patients directly for the therapy (which is very unusual in a true clinical trial). It’s imperative for physicians to appropriately educate patients about the possible downsides of unproven stem cell therapies being conducted outside of a true controlled clinical trial setting.

In conclusion, stem cell-based therapies have intriguing potential, but this field is still in its infancy. In the last several years, ESC-, iPSC-, and somatic stem cell-based therapies have advanced from in vitro and animal models to human trials with limited efficacy data. The major limitation of applying stem cell-based therapies to patients with AMD and similar pathologies is the chronic and complex disease process. For example, years of oxidative stress, an impaired inflammatory state with complement activation, and aging with choriocapillaris atrophy and ischemia create a microenvironment in AMD that challenges successful tissue replacement, engraftment and survival. Furthermore, given the polarity of RPE cells, transplanting sheets of cells with a scaffold, instead of suspensions, may be more physiologic, and some groups are consequently developing this concept further. Furthermore, surgical technique and immunosuppression will require additional clarification. REVIEW

Peter Bracha, MD, is chief resident and Thomas A. Ciulla, MD, MBA, is a volunteer clinical professor of ophthalmology at Indiana University School of Medicine. Dr. Ciulla also serves on the board of directors of Midwest Eye Institute and has an employment relationship with Spark Therapeutics. Neither Dr. Bracha nor Dr. Ciulla have financial interests in the subject matter.

1. Schwartz SD, Hubschman JP, Heilwell G, et al. Embryonic stem cell trials for macular degeneration: A preliminary report. Lancet 2012379:9817:713-20.

2. Schwartz S, Regillo CD, Lamet BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet 2015385:9967:509-16.

3. Schwartz, SD, Tan G, Hosseini H, Nagiel A. Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years. Invest Ophthalmol Vis Sci 201657:5:1-9.

4. Song, WK, Park KM, Kim HJ, et al. Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: Preliminary results in Asian patients. Stem Cell Reports 20154:5:860-72.

5. da Cruz L, Fynes K, Georgiadis O, et al. Phase I clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol 2018. 36:4:328-337.

6. Garber K. RIKEN suspends first clinical trial involving induced pluripotent stem cells. Nat Biotechnol 201533:9:890-1.

7. Chakradhar S. An eye to the future: Researchers debate best path for stem cell-derived therapies. Nat Med 201622:2:116-9.

8. Mandai M. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. N Engl J Med 2017376:11:1038.

9. Jonas JB. Intravitreal autologous bone marrow-derived mononuclear cell transplantation: a feasibility report. Acta Ophthalmol 200886:2:225-6.

10. Jonas JB. Intravitreal autologous bone-marrow-derived mononuclear cell transplantation. Acta Ophthalmol 201088:4:e131-2.

11. Park SS, Bauer G, Abedi M, et al. Intravitreal autologous bone marrow CD34+ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings. Invest Ophthalmol Vis Sci 201456:1:81-9.

12. Siqueira RC, Messias A, Voltarelli JC, et al. Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. Retina 201131:6:1207-14.

13. Siqueira RC, Messias A, Voltarelli JC, et al. Resolution of macular oedema associated with retinitis pigmentosa after intravitreal use of autologous BM-derived hematopoietic stem cell transplantation. Bone Marrow Transplant 201348:4:612-3.

14. Siqueira RC, Rubens C, Siqueira AM, Gurgel VP, et al. Improvement of ischaemic macular oedema after intravitreal injection of autologous bone marrow-derived haematopoietic stem cells. Acta Ophthalmol 201593:2:e174-6.

15. Kim JY, You YS, Kim SH, et al. Epiretinal membrane formation after intravitreal autologous stem cell implantation in a retinitis pigmentosa patient. Retin Cases Brief Rep 201711:3:227-231.

16. Leung EH, HW Flynn, TA Albini, et al. Retinal detachment after subretinal stem cell transplantation. Ophthalmic Surg Lasers Imaging Retina 201647:6:600-1.

17. Kuriyan AE, TA Albini, JH Townsend, et al. Vision loss after intravitreal injection of autologous “stem cells” for AMD. N Engl J Med 2017376:11:1047-1053.


Not all hope is lost. Currently, there’s a team of surgeons in Pittsburgh who hope to be able to transplant an entire eye by 2026! Thanks to advances in technology, new medicinal drugs, and trials in (safe) animal experiments, this team is close to taking a healthy, intact eye from a donor and implanting it into a receiver.

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We offer a discount of 20% off designer eyewear & exam fees when you use this code: GOULD20 (Not to be combined with other discounts or insurance. Can’t be used for Maui Jim or contact lens fitting exam).


Retina Problems And Retinal Disease: Q&A

Q: I had detached retinas in both eyes. I regained sight in my right eye but not in my left eye. I was wondering if there are any new procedures to help me. I have a lot of trouble with glare, and my left eyelid has begun to droop (congenital ptosis).

I was told that it would not be a good idea to get an eye transplant, but I feel that there must be something that can be done. If you have any information for me I would really appreciate it. — C.T., New Mexico

A: Long-standing retinal detachments are typically not reparable, even with the newer techniques of retina surgery. There is no such thing as an eye transplant, only a cornea transplant, and this wouldn&apost help the retinal detachment.

Tinted contact lenses or eyeglasses with photochromic lenses or other tinted lenses sometimes can help reduce glare. — Dr. Slonim

Watch this video on how a microchip implanted in the eye can restore some sight.

Q: In 1972 I was accidentally shot in my left eye with a BB. Cataracts formed in the eye, and in 1976-77 were removed. Would a lens transplant help get my vision back? As of now I can see maybe 5 percent of light.

The last time I went to an eye doctor, he said I also had a detached retina in the left eye. Since I don&apost use the left eye, is there any need to reattach the retina? — G.G., Arkansas

A: If the retinal detachment is the cause of the decreased vision (as I expect it probably is), then a lens implant will not help the vision. Retinal detachment surgery performed many years after the injury probably will not be successful. — Dr. Slonim

Q: How does diabetes affect your eyes? — L.L., Connecticut

A: Diabetes causes problems in the retina with what are collectively called microvascular abnormalities. The small blood vessels develop microaneurysms and leak blood. New blood vessel growth (neovascularization

) occurs. Unfortunately, these blood vessels are weak and also leak. These leaks (hemorrhages) can cause irreversible damage to the retina, with subsequent vision loss.

Patients with controlled diabetes do better than those with uncontrolled diabetes. However, even the diabetic who is under perfect control can still develop diabetic retinopathy — hence, the need for yearly retinal exams. — Dr. Slonim

Q: I had a retinal detachment some years ago that was mended with a "buckle." Now my vision is blurry sometimes, good other times. I also have allergies. What do you think causes the blurriness? — H.L., Arizona

A: It could be a number of things. Need some background and medical/surgery history. Could be a cataract. After all, you did have a scleral buckle in the past. — Dr. Slonim

Q: My eye doctor said I have a nebus and is sending me to a specialist. What is a nebus? — J.A., Florida

A: Probably nevus, which is the same as a pigmented freckle. Typically seen on the retina. The specialist will just offer an opinion or possibly photograph it to follow it in the future (a picture is worth a thousand words).

Just like any pigmented freckle on the skin, we watch pigmented retinal nevi to make sure they don&apost change their characteristics (e.g., size, shape, elevation, etc.) — Dr. Slonim

Q: I was born deaf due to maternal rubella. I was told that my iris color has flaked off because of the disease. I would like to know more information on that. — C.E.M., Georgia

A: Typically, rubella causes a retinitis (inflammation of the retina) with a "salt-and-pepper" appearance in the retina, which represents a mottling of the retinal pigment epithelium (pigmented layer below the retina). This condition may not affect vision at all. I am unaware of iris color changes as a result of rubella. — Dr. Slonim

Q: Can age cause your eye to have a hole in it behind the cornea? — Laura, Alabama

A: The hole "behind the cornea" is the pupil, which is an opening in the iris that allows light to pass through to the retina.

Retinal holes are possible and occur with a greater frequency as we get older.

Macular holes occur when small holes develop in the macula

. This can seriously affect one&aposs central vision while the peripheral portion of the retina remains intact and normal. — Dr. Slonim

Q: I have an eye disease called juvenile X-linked retinoschisis, plus congenital horizontal nystagmus. Could you give me any information on it? — R.R., Ontario, Canada

A: Retinoschisis is a splitting of the internal layers of the retina. The disease juvenile X-linked retinoschisis refers to a condition that is hereditary and usually presents with decreased vision during the first decade of life.

Frequently the splitting of the retinal layers occurs in the central retina (foveal area) and also in the periphery.

A nystagmus is a rhythmic (sometimes jerky) movement of the eyes. Congenital horizontal nystagmus refers to a movement which is in the horizontal plane (to the left and right) that is present at birth or found very early in life. — Dr. Slonim

Q: My left eye is seeing straight lines as wavy. The vision in that eye also tends to have blind spots come in and out, like things are morphing. What is this condition, and is there a treatment for it? — R.Z., California

A: If straight lines are wavy, then you need to see an ophthalmologist (probably a retinal specialist) to rule out a problem in your macula or other ocular structures. — Dr. Slonim

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