炎症与年龄相关性黄斑变性

近年来炎症与年龄相关性黄斑变性（AMD）的关系受到关注，主要包括与炎症相关的免疫分子与AMD的关系，如补体系统和炎症相关基因、单核细胞趋化蛋白（MCP）、C反应蛋白（CRP）等，以及炎症与AMD病理改变的关系如视网膜色素上皮细胞（RPE）损伤、玻璃膜疣以及脉络膜新生血管形成（CNV）等。     

脂肪干细胞体外诱导获得RPE样细胞及其治疗AMD相关研究进展

年龄相关性黄斑变性（age-related macular degeneration,AMD）是一种随年龄增长而发病率逐渐升高的黄斑部疾病.主要由视网膜色素上皮（retinal pigment epithelium,RPE）和视网膜退行性变引起的不可逆性中心视力下降.人类脂肪干细胞（adipose-derived stem cells,ADSC）具有多向分化潜能.近年研究发现,ADSC联合视网膜细胞诱导因子可体外诱导ADSC向RPE细胞分化,并表达RPE细胞的标志.相关动物模型显示,由ADSC分化而来的RPE样细胞移植后可参与视网膜重建及修复.ADSC移植为AMD的治疗提供了新思路.     

高血压和心血管病与年龄相关性黄斑变性

目的：报告一项关于新生血管性与非新生血管性年龄相关性黄斑变性（AMD）危险因素的对照研究及其与系统性高血压和心血管病的关系。方法：有或无新生血管和非新生血管性AMD患者来源于New York(NY)大都市区的11个眼科诊所。收集全面的资料包括：（1）标准化的采访过程;（2）血压的测量;（3）血液样品的采集。病例及其对照通过眼底照相的分级进行分类。应用多元回归分析法对其相关性进行评估。结果：对1222套可用照片进行分类,结果包括新生血管病例组（n=182)、非新生血管病例组（n=227)和对照组（n=235)。新生血管性AMD与以下因素呈正相关：舒张压高于95mm Hg(优势比[OR]=4.4,患者自报应用强效的抗高血压药物（OR＝2．1）,内科医生报告的高血压病史（OR＝1．8）,应用抗高血压药物（OR＝2．5）,自报的以及医生共同报告的相符合的高血压及其治疗资料（OR＝1．7）,高密度脂蛋白水平（OR＝2．3）和饮食中的胆固醇水平（OR＝2．2）。非新生血管性AMD与高血压或胆固醇水平无相关性。未发现任一AMD类型与其他种类型的高血压或心血管病之间有关。结论：这些发现提示新生血管性AMD与中、重度高血压,尤其与接受过抗高血压治疗有关。也支持新生血管性和非新生血管性AMD可能存在不同发病机制的假说,以及新生血管性AMD和高血压病有相似的系统性过程的假说。     

色素上皮源性因子在眼科研究中的进展

色素上皮源性因子（PEDF）最初是在胎儿视网膜色素上皮（RPE）细胞条件培养基中发现的一种神经营养因子。PEDF属于丝氨酸蛋白酶抑制剂超家族，是具有神经保护与抑制新生血管的神经营养因子，也是维持角膜、玻璃体无血管状态的主要细胞因子。PEDF的改变与多种眼病相关，尤其是视网膜脉络膜血管性、退行性疾病，也是治疗这类疾病的靶点之一。就PEDF的结构、功能以及在眼科方面的研究作一综述。     

ARMS2在人眼视网膜色素上皮细胞中的表达

年龄相关性黄斑变性(age-related macular degeneration,AMD)是一种累及黄斑部神经视网膜、视网膜色素上皮(retinal pigment epithelium,RPE)层及脉络膜并导致视力进行性损害的严重眼病,是老年人致盲的主要原因[1-2],在中国的发病率呈逐年上升的趋势.AMD是一种具有高度遗传异质性的疾病,基因遗传学研究已经证实AMD易感基因2(AMD susceptibility gene 2,ARMS2)与AMD的发生有显著相关性,而RPE的“老化”被认为是AMD发生的初始事件,研究表明黄斑部及周边部RPE细胞的结构及功能均存在异常.本研究通过原代培养RPE细胞,观察ARMS2在黄斑部及周边部RPE细胞中转录及蛋白水平的表达情况,探讨其在AMD发病过程中的作用.     

基于电子化信息平台的新生血管性年龄相关性黄斑变性真实世界研究进展

年龄相关性黄斑变性（AMD）是目前全球致盲的主要病因之一。抗血管内皮生长因子（Anti-VEGF）疗法已成为新生血管性AMD的一线治疗方案。考虑到抗VEGF药物的费用昂贵，患者需要长期甚至终身接受反复抗VEGF注射治疗，了解真实世界中抗VEGF的治疗情况，对于指导临床实践、改善患者诊疗路径乃至卫生决策都十分重要。近年来基于电子化信息平台的新生血管性AMD数据分析研究向我们展现了不同国家和地区新生血管性AMD的流行病学、真实世界抗VEGF的治疗情况以及医疗支出等，笔者就此作一综述。     

老年性黄斑变性光学相干断层扫描观察

目的 观察萎缩型，渗出型老年黄斑变性（Age-related macular degeneration AMD）患者的光学相干断层扫描图像特征。比较光学相干断层扫描（Optical Coherence Tomography OCT）和荧光血管造影（Fluorescein angiography FFA）的特点，对脉络膜新生血管（Choroidal neovascularization CNV）进行OCT分型。方法 经FFA确诊的AMD57例76只眼进行OCT检查。结果 AMD患者色素上皮萎缩，软性玻璃膜疣，神经上皮和色素上皮脱离具有特有的OCT特征，OCT图像中视网膜神经上皮增厚、隆起反映视网膜下，视网膜层间积液。神经上皮或色素上皮（Retinal pigment epithelium，RPE）隆起，其下低反射区反映神经上皮或RPE层脱离。CNV的OCT图像分为边界清晰的CNV，边界模糊的CNV，纤维血管性RPE脱离。FFA中的典型性CNV相当于OCT图像中边界清晰CNV，隐匿性CNV相当于OCT图像中边界模糊CNV和纤维血管性RPE脱离。结论 OCT能特征性显示AMD中视网膜神经上皮隆起，视网膜层间积液，出血，神经上皮和RPE的脱离，且显示不同类型CNV的OCT特征。     

自体色素上皮细胞移植

随着视网膜色素上皮（RPE）细胞移植研究的不断深入，人们对于它可用于治疗老年性黄斑变性（ARMD）等视网膜色素上皮变性类疾病寄予了希望。但异种或同种异体的RPE细胞移植总不能完全避免免疫排斥反应，所以人们开始研究自体色素上皮细胞的移植，本对近年来有关自体色素上皮细胞（包括虹膜色素上皮细胞和视网膜色素上皮细胞）的形态、功能、取材及移植等方面的研究作一综述。     

玻璃体腔注射抗血管内皮生长因子药物治疗年龄相关性黄斑变性引起的视网膜色素上皮撕裂的特点分析

目的 总结分析玻璃体腔注射抗血管内皮生长因子（VEGF）药物治疗年龄相关性黄斑变性（AMD）引起的视网膜色素上皮（RPE）撕裂的临床特点.方法 文献分析.通过PubMed和中国生物医学文献光盘数据库检索系统查阅玻璃体腔注射抗VEGF药物治疗AMD引起RPE撕裂的相关文献,统计分析患者的年龄、视力、RPE撕裂的发生率及发生部位、发生RPE撕裂前玻璃体腔注药的次数及周期、玻璃体腔注射的药物种类、撕裂发生的危险因素等.结果 最终有35篇文献（7879眼）纳入研究.发生RPE撕裂的患者的平均年龄为78.6岁（59～96岁）,平均玻璃体腔注药1.6次（1～次）,撕裂发生后至初次诊断的平均时间间隔为34.8 d（1 d～4个月）.玻璃体腔注射任何抗VEGF药物均可能会引起RPE的撕裂,RPE撕裂基本都发生在平行于色素上皮脱离（PED）的边缘.玻璃体腔注药引起RPE撕裂的发生率为0.1%～7.5%,平均1.9%.初次确诊为RPE撕裂时,与撕裂发生前相比,绝大多数患者的视力有提高或保持稳定（81.4%）.经过平均94.9 d的随访,绝大多数患者的最终视力保持稳定或有提高（83.3%）.大范围的血管性PED是RPE撕裂发生的危险因素,当血管性PED的高度＞400μm时,玻璃体腔注药后发生RPE撕裂的危险性明显增加.结论 玻璃体腔注射抗VEGF药物治疗AMD可能会引起RPE的撕裂,但发生率较低,且RPE撕裂对大多数患者的视力无明显影响.大范围的、高的血管性PED是RPE撕裂发生的危险因素.     

视网膜色素上皮细胞移植的研究

视网膜色素上皮细胞（RPE）是位于视网膜感光器细胞和和脉络膜之间的一层单层细胞。本文介绍了RPE细胞的分离、培养和内、外路两种不同的手术方法。从术后活体和组织学检查表明，视网膜下腔是一免疫赦免区域。通过对首次异体移植培养的胎儿RPE细胞病例的临床随访显示，所移植的RPE细胞在黄斑区均能存活，并且具有注视功能。术后囊样黄斑水肿是最主要的并发症，是宿主免疫排斥反应的结果。因此预防和处理移植物的免疫排斥，是手术成功的关键。     

Long-term outcome of RPE allografts in non-immunosuppressed patients with AMD.

PURPOSE: To determine the long-term outcome of human retinal pigment epithelium (RPE) transplants in patients with advanced age-related macular degeneration (AMD). METHODS: Using pars plana microsurgical techniques, RPE allografts were transplanted subretinally to four groups of AMD patients: five patients received organized patch transplants after removal of choroidal neovascular membranes, four got small patch transplants in dry AMD; suspensions of RPE cells were transplanted in five cases with dry AMD, and two patients with RPE tears. None received immunosuppression. Transplants were followed for 24-38 months by biomicroscopy, fundus photography, SLO microperimetry, and fluorescein angiography. Rejection was defined as loss of visual function over the transplant, development of an exudative response (subretinal fluid with or without neovascularization), fluorescein leakage, and disruption, depigmentation, or encapsulation of the transplant. RESULTS: Four of 16 transplants (25%) presented no clinical signs of rejection. Three of the four small patch transplants remained pigmented and essentially unchanged after 30-32 months. Clinical signs of graft rejection appeared within three months in all cases of neovascular AMD (disrupted blood-retinal barrier, BRB), but after 6-20 months in five of nine eyes with non-exudative AMD (intact BRB). CONCLUSIONS: Subretinal human RPE allografts present a high rejection rate (75%) without immunosuppression. However, small extrafoveal transplants remained unchanged in shape, size and color for more than two years in non-exudative AMD. A disrupted BRB is likely to enhance graft rejection, which occurs earlier in exudative than in non-exudative AMD.     

Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration

PURPOSE: To improve visual function by retinal pigment epithelial (RPE) cell transplantation and systemic immunosuppression at the time of surgical removal of subfoveal choroidal neovascularization in exudative age-related macular degeneration (AMD). DESIGN: An interventional case series of RPE transplantation in exudative AMD. METHODS: Twelve patients (one eye only) underwent subfoveal membranectomy with transplantation of a sheet of adult human allogeneic RPE cells at a single institution and were followed for one year. Eligibility criteria included age >60, best-corrected acuity < or =20/63 and subfoveal neovascularization < or =9 disk areas on preoperative fluorescein angiography. All patients were started on triple immunosuppression postoperatively. The primary outcome measure was best-corrected vision, with contrast sensitivity and reading speed as secondary outcome measures. RESULTS: The best-corrected visual acuity (P = .085), contrast sensitivity (P = .204), and the reading speed (P = .077) did not change significantly at one year compared with preoperative values. Transplants showed no signs of rejection in patients who were able to continue the immunosuppressants for six months. Postoperative surgical complications included cataract progression requiring surgery (three of eight phakic eyes), retinal detachment (three eyes), intraoperative retinal breaks (two eyes), and macular pucker (two eyes). None of the patients developed cystoid macular edema on postoperative fluorescein angiography or postoperative inflammation. CONCLUSIONS: A sheet of adult human allogeneic RPE can be transplanted into the subretinal space in AMD patients at the time of subfoveal membranectomy. Systemic immune suppression appeared to prevent rejection of the transplanted tissue, but did not lead to an improvement in visual function.     

Transplantation of RPE in age-related macular degeneration: Observations in disciform lesions and dry RPE atrophy

A study was carried out to investigate whether human RPE allografts are tolerated or rejected in the subretinal space and to determine the feasibility of RPE transplantation in subjects with age-related macular degeneration (AMD). Methods: Patches of human fetal RPE (13–20 weeks of gestational age) were transplanted into the subretinal space of five patients after surgical removal of subfoveal fibrovascular membranes, and to four subjects with dry geographic atrophy. Suspensions of RPE cells were transplanted to four other patients with nonexudative AMD. Results were evaluated with clinical ophthalmological examination, SLO microperimetry and fluorescein angiography over 8–20 months. Results: In disciform lesions, RPE transplants developed macular edema and fluorescein leakage concomitant with gradual reduction of visual acuity, implying host-graft rejection, over 1–6 months. In geographic atrophy, three of four transplants showed little change in shape and size after 12 months (one transplant was slowly rejected). In non-exudative AMD, RPE suspension transplants showed no evidence of rejection and were associated with the disappearance of drusen; visual acuity remained stable and SLO microperimetry confirmed retinal function over the transplanted area. Conclusion: Human RPE allografts are not invariably rejected in the subretinal space without immunosuppression. The rejection rate is lower in nonexudative than in neovascular AMD. An intact blood-retinal barrier is likely to protect against rejection. It is technically feasible to transplant human RPE into the submacular space without adversely affecting visual function in nonexudative AMD over relatively long periods of timeThis work was supported by grants from the Swedish Medical Research Council (B96-12X-11561-01A) and the Crown Princess Margareta Foundation, Stockholm, Sweden.     

Retinal pigment epithelium in the pathogenesis of age‐related macular degeneration and photobiomodulation as a potential therapy?

The retinal pigment epithelium (RPE) comprises a monolayer of cells located between the neuroretina and the choriocapillaries. The RPE serves several important functions in the eye: formation of the blood‐retinal barrier, protection of the retina from oxidative stress, nutrient delivery and waste disposal, ionic homeostasis, phagocytosis of photoreceptor outer segments, synthesis and release of growth factors, reisomerization of all‐trans‐retinal during the visual cycle, and establishment of ocular immune privilege. Age‐related macular degeneration (AMD) is the leading cause of blindness in developed countries. Dysfunction of the RPE has been associated with the pathogenesis of AMD in relation to increased oxidative stress, mitochondrial destabilization and complement dysregulation. Photobiomodulation or near infrared light therapy which refers to non‐invasive irradiation of tissue with light in the far‐red to near‐infrared light spectrum (630–1000 nm), is an intervention that specifically targets key mechanisms of RPE dysfunction that are implicated in AMD pathogenesis. The current evidence for the efficacy of photobiomodulation in AMD is poor but its safety profile and proposed mechanisms of action motivate further research as a novel therapy for AMD.     

Autologous subretinal transplantation of cultivated porcine iris pigment epithelial cells (IPE)

BACKGROUND: Subretina transplantation of epithelium may be a therapeutic option for surgical treatment of age-related macular degeration (AMD). Various experimental data have demonstrated that homologous transplantation of retinal pigment epithelium (RPE) can prevent photoreceptor deterioration. However, most investigators experienced immunogenic graft rejection when using homologous pigmented cells for grafting. Autologous cells were soon considered as an alternative for subretinal grafting. Particularly iris pigment epithelium (IPE) appeared suitable to replace homologous RPE for it embryogenetic similarity and its simple availability. Recent studies have shown, that IPE is capable of taking over functions of RPE in maintaining retinal metabolism. the purpose of this study was to evaluate if autologous IPE cells would survive when being transplanted subretinally. In addition, immunogenic reponses to the presence of "foreign" iris pigment cells needed to be excluded. MATERIALS AND METHODS: Iris tissue was obtained by peripheral iridectomy in the anesthetized pig. Sheets of pigment iris epithelium were separated from the specimens and transferred into tissue culture. After the cells had been grown to confluency, cell suspensions were injected into the subretinal space of the donor animal's fellow eye. After 4 weeks, the grafted eye was enucleated and examined histologically.. RESULTS: The histological exam revealed that the graft cells had survived in the subretinal space. No evidence of immunogenic rejection was observed. CONCLUSION: Autologous IPE-cells can survive in the host's sub-retinal space without creating inflammatory reactions. Transplanted IPE appears to interact with photoreceptor outer segments.     

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular (NV-AMD) or non-neovascular (NNV-AMD). Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD (Geographic Atrophy). In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs (e.g., anti-VEGF) are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells (hESC-RPE) and from induced pluripotent stem cells (iPSC-RPE) has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed.     

Transplantation of the RPE in AMD

The retinal pigment epithelium (RPE) maintains retinal function as the metabolic gatekeeper between photoreceptors (PRs) and the choriocapillaries. The RPE and Bruch's membrane (BM) suffer cumulative damage over lifetime, which is thought to induce age-related macular degeneration (AMD) in susceptible individuals. Unlike palliative pharmacologic treatments, replacement of the RPE has a curative potential for AMD. This article reviews mechanisms leading to RPE dysfunction in aging and AMD, laboratory studies on RPE transplantation, and surgical techniques used in AMD patients. Future strategies using ex vivo steps prior to transplantation, BM prosthetics, and stem cell applications are discussed. The functional peculiarity of the macular region, epigenetic phenomena leading to an age-related shift in protein expression, along with the accumulation of lipofuscin may affect the metabolism in the central RPE. Thickening of BM with age decreases its hydraulic conductivity. Drusen are deposits of extracellular material and formed in part by activation of the alternative complement pathway in individuals carrying a mutant allele of complement factor H. AMD likely represents an umbrella term for a disease entity with multifactorial etiology and manifestations. Presently, a slow progressing (dry) non-neovascular atrophic form and a rapidly blinding neovascular (wet) form are discerned. No therapy is currently available for the former, while RPE transplantation and promising (albeit non-causal) anti-angiogenic therapies are available for the latter. The potential of RPE transplantation was demonstrated in animal models. Rejection of allogeneic homologous transplants in patients focused further studies on autologous sources. In vitro studies elucidated cell adhesion and wound healing mechanisms on aged human BM. Currently, autologous RPE, harvested from the midperiphery, is being transplanted as a cell suspension or a patch of RPE and choroid in AMD patients. These techniques have been evaluated from several groups. Autologous RPE transplants may have the disadvantage of carrying the same genetic information that may have led to AMD manifestation. An intermittent culturing step would allow for in vitro therapy of the RPE, its rejuvenation and prosthesis of BM to improve the success RPE transplants. Recent advances in stem cell biology when combined with lessons learned from studies of RPE transplantation are intriguing future therapeutic modalities for AMD patients.     

Hyperreflective Foci,Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration,Include Transdifferentiated Retinal Pigment Epithelium

PurposeBy optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia.MethodsIn clinical OCT (61 eyes, 44 patients with AMD, 79.4 ± 7.7 years; 29 female; follow-up = 4.7 ± 0.9 years), one HRF type, RPE plume (n = 129 in 4 morphologies), was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy, 6; neovascular AMD, 3). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semiquantitatively by one observer (none, some cells, all cells).ResultsPlume morphology evolved over time and many resolved (40%). Trajectories of RPE plume and cellular debris paralleled Müller glia, including near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Müller glia remained CRALBP positive. Plume cells approached and contacted retinal capillaries.ConclusionsHRF are indicators not predictors of overall disease activity. Gain and loss of function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial–mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.     

The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD

The retinal pigment epithelium (RPE) is a highly specialized, unique epithelial cell that interacts with photoreceptors on its apical side and with Bruch's membrane and the choriocapillaris on its basal side. Due to vital functions that keep photoreceptors healthy, the RPE is essential for maintaining vision. With aging and the accumulated effects of environmental stresses, the RPE can become dysfunctional and die. This degeneration plays a central role in age-related macular degeneration (AMD) pathobiology, the leading cause of blindness among the elderly in western societies. Oxidative stress and inflammation have both physiological and potentially pathological roles in RPE degeneration. Given the central role of the RPE, this review will focus on the impact of oxidative stress and inflammation on the RPE with AMD pathobiology. Physiological sources of oxidative stress as well as unique sources from photo-oxidative stress, the phagocytosis of photoreceptor outer segments, and modifiable factors such as cigarette smoking and high fat diet ingestion that can convert oxidative stress into a pathological role, and the negative impact of impairing the cytoprotective roles of mitochondrial dynamics and the Nrf2 signaling system on RPE health in AMD will be discussed. Likewise, the response by the innate immune system to an inciting trigger, and the potential role of local RPE production of inflammation, as well as a potential role for damage by inflammation with chronicity if the inciting trigger is not neutralized, will be debated.     

The retinal pigment epithelium: Development,injury responses,and regenerative potential in mammalian and non-mammalian systems

Diseases that result in retinal pigment epithelium (RPE) degeneration, such as age-related macular degeneration (AMD), are among the leading causes of blindness worldwide. Atrophic (dry) AMD is the most prevalent form of AMD and there are currently no effective therapies to prevent RPE cell death or restore RPE cells lost from AMD. An intriguing approach to treat AMD and other RPE degenerative diseases is to develop therapies focused on stimulating endogenous RPE regeneration. For this to become feasible, a deeper understanding of the mechanisms underlying RPE development, injury responses and regenerative potential is needed. In mammals, RPE regeneration is extremely limited; small lesions can be repaired by the expansion of adjacent RPE cells, but large lesions cannot be repaired as remaining RPE cells are unable to functionally replace lost RPE tissue. In some injury paradigms, RPE cells proliferate but do not regenerate a morphologically normal monolayer, while in others, proliferation is pathogenic and results in further disruption to the retina. This is in contrast to non-mammalian vertebrates, which possess tremendous RPE regenerative potential. Here, we discuss what is known about RPE formation during development in mammalian and non-mammalian vertebrates, we detail the processes by which RPE cells respond to injury, and we describe examples of RPE-to-retina and RPE-to-RPE regeneration in non-mammalian vertebrates. Finally, we outline barriers to RPE-dependent regeneration in mammals that could potentially be overcome to stimulate a regenerative response from the RPE.