Morphological recovery in the reattached retina

After experimental retinal detachment in the cat, a number of morphological changes take place in retinal and RPE cells. Following reattachment, the ultrastructural relationship between the photoreceptors and the RPE is re-established, but it does not return to the predetachment state even after short detachment episodes coupled with prolonged recovery periods. All of the reattached retinae show some degree of abnormality, ranging from subtle changes in photoreceptor ultrastructure to dramatic degenerative effects in the outer retina. Abrupt transitions in morphology from one reattached area to an adjacent area are not unusual. Photoreceptor recovery varies widely between animals, and between adjacent regions within the same retina. Ensheathment of outer segments by RPE apical processes is abnormal. In some reattached areas rod outer segment dimensions and disc structure are near normal as is the displacement rate of rod outer segment discs. In others, especially in areas of RPE or Müller cell proliferation and hypertrophy, the outer segments are shortened or absent completely, and there is a reduction of cell bodies in the outer nuclear layer. In some retinae, recovery in cones is inferior to that in rods. At short detachment durations (less than 1 wk) morphological recovery in the reattached retina is optimal while at long intervals (greater than 1 month) recovery is poor. The changes at the photoreceptor-RPE interface identified in the reattached cat retina probably have adverse effects on visual recovery when they occur within the human macula.     

实验性视网膜脱离的病理改变及细胞增生

目的:探讨实验性视网膜脱离的病理变化和细胞增生。方法:成年白化病兔32眼在间接检眼镜直视下,先抽取玻璃体液0.5mL软化眼球,用50nm玻璃微管在下方6:00赤道部部位刺入视网膜造成裂孔并注射生理盐水0.5mL于视网膜下间隙。术后0.5,1,3,6,24h;3,7d和14d摘除眼球作组织学观察并以免疫组织化学的方法检测视网膜下细胞增生。结果:32只兔眼术后均发生视网膜脱离,视网膜脱离范围3:00～9:00(髓腺下方视网膜均脱离)。自发性复位的时间在3～14d,组织学切片显示,3d可见视网膜色素上皮细胞积聚团,7dRPE细胞增生肥大呈巨噬细胞样改变,14dRPE多层化改变,并见巨噬细胞样RPE来源于单层的RPE,游离RPE层后,吸附于脱离的光感受器细胞外节;3d增生细胞核抗原即表达阳性,增生细胞表达角蛋白阳性。结论:在此模型中,RPE细胞表现出细胞增生,巨噬细胞样细胞也来源于RPE。     

ANATOMICAL RECOVERY FOLLOWING RETINAL DETACHMENT

The histological findings in experimental retinal detachment and reattachment of the cat retina are described. Loss of photoreceptor outer segments, mounding of the apical surface of the retinal pigment epithelium, and loss of the apical villi of the retinal pigment epithelium are prominent features of the detached cat retina. Reattachment within the first week of retinal detachment is followed by good photoreceptor regeneration and orientation. Longer term detachment of 2 to 6 weeks results in poorer photoreceptor outer segment regeneration and orientation 4 weeks following reattachment surgery. These experimental results are consistent with clinical data concerning visual recovery following retinal reattachment surgery.     

Opsin distribution and protein incorporation in photoreceptors after experimental retinal detachment.

The distribution of opsin was examined immunocytochemically after experimental retinal detachment in adult cats. Retinal detachments were produced by injecting fluid between the retinal pigment epithelium and neural retina. One to 60 days later the animals were killed. Tissue areas from detached and attached retinal regions from the eye with the detached retina, as well as normal (control) retinas, were processed for post-embedding light and electron microscopic immunocytochemistry. In normal and attached retinal regions, anti-opsin labeled the outer segments and Golgi apparatus most heavily, although the entire photoreceptor plasma membrane was labeled at a low level. Beginning at 2 days after retinal detachment, immunolabeling increased in the photoreceptor inner segment, cell body and synaptic terminal plasma membranes. This pattern of anti-opsin labeling continued at all intervals up through the 60-day detachment time-point. Injection of radiolabeled amino acid in detachments from 1 to 30 days show that radiolabeled protein is still transported to the truncated outer segments of the photoreceptor cells. In addition, these outer segment disks label with anti-opsin. These data imply that opsin continues to be transported and incorporated into the outer segments of photoreceptors showing severe degeneration as a result of long-term detachment from the RPE.     

Rhodopsin regeneration in the normal and in the detached/replaced retina of the skate.

The bleaching and regeneration of rhodopsin in the skate retina was studied by means of fundus reflectometry, both in the normal eyecup preparation and after the retina had been detached and then replaced on the surface of the pigment epithelium (RPE). After bleaching virtually all the rhodopsin in the retinal test area of the normal eyecup, more than 90% of the photopigment was reformed after about 2 hr in darkness; over most of this time course, rhodopsin density rose linearly at a rate of 0.875% min-1 with a half-time of 55 min. Detaching the retina from its pigment epithelium resulted in a number of abnormalities, both structural and functional. Histological examination of the detached/replaced (D/R) retina showed striking alterations in the structural integrity of the RPE cells at their interface with the neural retina. The cells appeared vacuolated and misshapen, and the apical processes of the RPE, which normally ensheath the receptor outer segments, were shredded and free of their association with the visual cells. These morphological changes, as well as dilution of the IRBP content of the subretinal space caused by separation of the tissues, appear to be the main factors contributing to the functional abnormalities in rhodopsin kinetics. But despite these abnormalities and the persistent detachment, the rate of regeneration and the amount of rhodopsin reformed after bleaching were reduced by less than 50% of their normal values. The fact that a significant fraction of the bleached rhodopsin was regenerated under these conditions indicates that 11-cis retinal formed in the RPE was able to traverse a much greater than normal subretinal space to reach the opsin-bearing photoreceptor membranes.     

N-cadherin expression in a rat model of retinal detachment and reattachment

PURPOSE: To observe the changes in N-cadherin expression in the retina after experimental retinal detachment (RD) and reattachment in the rat and to explore the role N-cadherin might play after RD. METHODS: Forty rat retinas were detached by transscleral injection of 1.4% sodium hyaluronate into the subretinal space. The eyes were enucleated at different time intervals (n = 5), followed by fixation, embedding, and sectioning. The differences in N-cadherin expression in the normal retina, detached retina, and spontaneously reattached retina were determined. Furthermore, an N-cadherin antagonist was injected in combination with 1.4% sodium hyaluronate into the subretinal space in another 10 eyes, in an attempt to demonstrate the role N-cadherin plays after RD. RESULTS: N-cadherin was not expressed in the RPE layer of the normal rat retina. After RD, intense immunolabeling of N-cadherin was seen in the RPE cells, the photoreceptors, and the outer limiting membrane (OLM). An increasing number of cytokeratin (CK)-positive cells likely to be RPE cells was found attached to the outer surface of the detached neural retina. Where the retina was reattached, the N-cadherin immunolabeling rapidly decreased. In eyes treated with an N-cadherin antagonist, the retinas appeared thinner than that in eyes without treatment, and the photoreceptor nuclei showed significantly loss. Moreover, CK-positive cells attached to the outer surface of the detached retina were markedly fewer in number. CONCLUSIONS: Increased expression of N-cadherin in the RPE cells, the photoreceptor cells, and the OLM of the retina after RD may contribute to RPE cell migration and photoreceptor survival. These changes could be reversed by retinal reattachment.     

实验性视网膜脱离及复位后视网膜色素上皮细胞抗增殖性细胞核抗原的表达

目的 观察视网膜脱离和复位过程中抗增殖性细胞核抗原(proiferating cell nuclear antigen, PCNA)表达的状况，以评价其在接触抑制机制中的意义。 方法 对72只猫眼行晶状体 囊外摘除和玻璃体切除手术。3周后，利用微穿刺技术制作视网膜脱离和复位动物模型，在不同时间取眼球并制成组织切片。采用免疫组织化学方法，观察视网膜脱离后视网膜色素上皮(retinal pigment-epithelium, RPE)细胞PCNA的表达。光镜下确定PCNA阳性的RPE细胞并量化增殖反应。采用方差分析(ANOVA)方法 ，对脱离组的脱离区和非脱离区及复位组复位区RPE细胞层PCNA的表达水平进行比较。 结果 在视网膜脱离后24 h，脱离组脱离区视网膜RPE细胞层出现PCNA阳性细胞 ，5～6 d达到高峰，20 d后逐渐回落。在复位组复位区，PCNA标记的RPE细胞明显少于脱离组脱离区。脱离组非脱离区视网膜很少有PCNA标记的RPE细胞。3组PCNA标记的RPE细胞数比较，差异有显著性的意义。 结论 视网膜脱离诱导RPE细胞增殖，而视网膜复位后这种增殖受到抑制。表明视网膜复位过程中，接触抑制的机制在发挥作用。（中华眼底病杂志，2003，19：20-23）     

Comparison of photoreceptor-specific matrix domains in the cat and monkey retinas

Two lectins, wheat germ agglutinin (WGA) and peanut agglutinin (PNA), were used to compare domains within the interphotoreceptor matrices (IPM) of the cat and monkey, two species where the morphological relationship between the retinal pigment epithelium (RPE) and photoreceptors is distinctly different. In the monkey, PNA labeling was heaviest over the cone outer segments and a discrete region of the interphotoreceptor matrix bordering the cone inner and outer segments--a region which has been termed the cone matrix sheath. Near the apical border of the RPE, the outer margin of the PNA-labeled matrix is surrounded by a circular array of apical microvilli. In the cat retina, PNA labeling was highest over a region of the IPM lying between the outer margin of the cone sheath processes and surrounding rod matrix. In contrast, intracellular labeling of cone inner and outer segments was sparse. The RPE apical processes forming the cone sheath were not labeled. In the monkey retina, WGA preferentially labeled rod outer segments and the region of the IPM around rod inner and outer segments. The cone matrix sheath was not preferentially labeled using this lectin. Rod inner segments and cone inner and outer segments were labeled moderately. In the cat retina, WGA labeling was dense over both rod outer segments and cone outer segments as well as the cone sheath. Rod and cone inner segments, as well as the IPM around both rods and cones, were moderately labeled. These observations suggest that the specialized processes arising from the apical surface of retinal pigment epithelial cells, together with photoreceptor-specific extracellular matrix domains, contribute to the formation of specific microenvironments around rod and cone photoreceptor cells.     

Ultrastructural changes in the retinal pigment epithelium of congenitally blind chickens

Pathological changes in the retinal pigment epithelium (RPE) in a strain of chickens having hereditary blindness and retinal degeneration were described at the ultrastructural level. Photoreceptors in the retinal degenerate (rd) chicken had previously been noted to degenerate within a week after hatching. Affected chicks have neural retinas that are morphologically comparable to normal animals prior to that time despite an obvious lack of vision. In the present study, no pathological changes were noted in rd RPE prior to the time of photoreceptor degeneration. However, while mitochondria in the normal chick's RPE underwent diurnal changes in morphology within a few days of hatching, pleomorphic or ring mitochondria were not seen with high frequency in the rd chick. After photoreceptors began degenerating, changes were seen in the rd RPE. By 2 weeks of age, we noted a reduction in the depth and number of basal infoldings, an increase in number and size of autophagic vacuoles and large whorls of membranous material within rd RPE cells. Membranous debris and what appeared to be broken off outer segments were seen in the subretinal space at that time. These phenomena became more prominent and prevalent with time. In 3-4 week old specimens, nearly intact outer segments were seen within RPE cytoplasm. At the same time very few intact outer segments were present on photoreceptors. After this time degenerative changes were seen in the RPE: a thinning of cells (apical to basal cell width), spreading out of cells (increased distance between intercellular junctional complexes), hypopigmentation of cells and presence of free cells in the sub-retinal space. Some RPE cells appeared in a rounded up configuration, bulging into the subretinal space and making junctional complexes with remaining photoreceptor inner segments or Mueller cell processes. Many RPE cells did appear to maintain their phagocytic abilities, as evidenced by presence of many microvilli and pinocytotic vacuoles in the apical cytoplasm.     

Prevention of rod disk shedding by detachment from the retinal pigment epithelium

The authors tested whether or not rod outer segment (ROS) disks are shed when the neural retina is detached from the retinal pigment epithelium (RPE). Adult Xenopus were injected with 3H-L-leucine. Later, when the distal disks of their ROSs were labeled with a band of 3H-leucine, their eyes were enucleated. Intact eyecups, eyecups with partially detached retinae, and retinae that were peeled completely away from the RPE were incubated in culture medium. Disk shedding was stimulated by changes in lighting, or the addition of 0.5 mM ouabain. Where the retina was attached, phagosomes in the RPE, and not the ROSs, contained most of the radiolabel. Where there was retinal detachment, ROSs were still heavily radiolabeled near their distal ends. It was concluded that mechanical retinal detachment prevents ROS disk shedding.     

Specialization of the interphotoreceptor matrices around cone and rod photoreceptor cells in the monkey retina, as revealed by lectin cytochemistry

The binding sites of two lectins, peanut agglutinin (PNA) and wheat germ agglutinin (WGA), in the interphotoreceptor matrix (IPM) and photoreceptor plasma membranes of the Japanese monkey (Macaca fuscata) retina were localized using a pre-embedding staining method with ferritin-conjugated (Fer) lectins as well as a postembedding staining method with fluorescence-labeled (FITC) lectins. FITC-PNA, but not WGA, stained cylindrical domains of the IPM around cone outer and inner segments, while the IPM around rods stained with FITC-WGA but not PNA. When the intact (not detached) retinal tissues were incubated with Fer-lectin, the lectin generally labeled neither the IPM nor photoreceptor plasma membranes, but labeled only those structures in detached portions occurring at the edges of occasional retinal tissue blocks. Thus, the neural retinas physically isolated from the retinal pigment epithelium (RPE) were utilized principally here. Ultrastructurally, the IPM in the intact retina consisted of granular and filamentous materials; the IPM in the isolated neutral retina also retained those components, although somewhat loosely organized, and the IPM around cones appeared to be preserved better than did the IPM around rods. Fer-PNA bound to the IPM associated with cones, but not rods; Fer-WGA bound to the rod- but not cone-associated IPM. The ferritin particles were found to lie close to the granular and filamentous materials. Those photoreceptor-associated IPMs extended to the apical surface of the RPE in detached portions or to the apical villi of the RPE which were frequently found in the isolated neural retinas. Also, Fer-PNA labeled the cone, but not rod, plasma membranes; Fer-WGA bound heavily to the plasma membranes of rod and cone outer segments, but sparsely to those of their inner segments. These results suggest that the IPM comprises chemically and physically differential domains specialized for cone and rod photoreceptor cells, and that these specialized IPM are structurally so stable that may be involved in isolating photoreceptor cells physicochemically from each other and in the interactions between the photoreceptors and the RPE, such as retinal adhesion.     

视网膜视细胞的成片移植

目的 探索用准分子激光切削技术制备视网膜单层细胞植片,经内入路视网膜下腔的单层视细胞成片移植。方法 用准分子激光对大鼠视网膜进行切削,制取单层视细胞植片,此后,按内入路手术方法进行了兔视网膜下腔的异种移植。结果 切削后所得视细胞植片由单层视细胞组成,结构完整,包括外丛状层、外核层和外节层;视细胞植片经明胶包埋后被准确植入宿主视网膜下腔中,移植术后第1,2天宿主观视网膜未能复位,呈脱离状态,移植物没能与视网膜色素上皮层相贴;移植后10天,宿主视网膜复位,视细胞移植片平铺于宿主视网膜下腔中,植片视细胞外节也宿主视网膜色素上皮层相贴;移植后10天,宿主视网膜复位,视细胞移植片平铺于宿主视网膜下腔中,植片视细胞外节与宿主视网膜色素上皮层相贴,未见明显免疫排异现象。结论 准分子激光制备单层视细胞植片方法简单、可行;初步观察到内入路单层视细胞成片移植后,视细胞植片能够在宿主视网膜下腔中以正常生理位置存活;视网膜下腔为理想的视网膜移植的受位。     

Morphological observations of the apical surface of chick retinal pigment epithelium

Chick embryonic retina was examined in order to investigate morphological changes of the apical portion of retinal pigment epithelial (RPE) cells. Whole retina and RPE sheets were observed by fluorescence microscopy (rhodamine-phalloidin preparation) and transmission electron microscopy. Photoreceptor cells had no inner and outer segments on the 8th day in ovo. The inner segments have been formed on the 15th day and the outer segments on the 19th day. RPE sheets had short and blunt apical processes on the 8th day, elongated and slender ones on the 15th day, and well-developed and melanin-containing processes on the 19th day. RPE of the 19th day had numerous bundles of actin filaments associated with melanin pigments in the basal portion of the apical processes and in the apical cytoplasm. In rhodamine-phalloidin preparations, intense fluorescence was localized in the RPE apical processes and cytoplasm on the 19th day. We concluded that RPE apical processes develop in accordance with the photoreceptor development.     

Tritiated uridine labeling of the retina: changes after retinal detachment.

As part of a study designed to examine the response of photoreceptor cells to outer segment injury (retinal detachment), the pattern of RNA labeling ([3H]uridine incorporation) has been determined in detached cat retinas. Retinas were experimentally detached from the adjacent cellular layer (the retinal pigment epithelium:RPE) by injecting fluid into the extracellular space between the retina and RPE. Twenty-four hours before the animals were killed they received intravitreal injections of [3H]uridine. Autoradiograms were prepared from plastic sections 1.0 micron thick taken from detached retinal regions and, because the detachments do not encompass all of the retina, from nearby attached retinal regions. Twenty-four hours after retinal detachment there is a decrease in labeling intensity of the photoreceptors and Müller's glia in the region of detachment (compared to cells in nearby attached regions). Seventy-two hours after retinal separation, the same result is obtained in the photoreceptors, but labeling intensity is greatly increased in both the nuclei and cytoplasm of Müller's glia. The decrease in [3H]uridine labeling of the photoreceptors correlates with a decreased staining intensity of the cytoplasm and ultrastructural signs of necrosis. The striking change in the pattern and intensity of labeling of the Müller cells precedes extensive hypertrophy of these cells and the appearance within their cytoplasm of numerous 10-nm diameter filaments. Two weeks, and also 1 month, after detachment the pattern and labeling levels are similar to those observed 1 day after retinal separation. These data suggest a highly localized change in metabolism because the change in RNA labeling is restricted to the region of detached retina.     

Retinal detachment in the cat: the outer nuclear and outer plexiform layers

The retinae of cats were surgically detached for 1/2 hr to 14 months, and the outer nuclear (ONL) and outer plexiform layers (OPL) were studied by light and electron microscopy. The longer the duration or the greater the height of detachment the more likely was the occurrence of cell death. Histologic signs of degeneration were present 1 hr after detachment. The number of photoreceptor nuclei in the ONL decreased significantly by 1 month. Loss of cells in the ONL occurred by necrosis and by the migration of photoreceptor cell bodies into the subretinal space. The OPL degenerated by the necrosis of cell processes and synaptic terminals and by the retraction of the synaptic terminals. By 2 weeks most synaptic terminals were necrotic or in the process of retracting. Photoreceptor synaptic contact with second order neurons was diminished by 30 days and was essentially absent by 50 days. Müller cells proliferated and hypertrophied; their nuclei and cell processes filled the intraretinal spaces left by the degenerating photoreceptors. In addition, Müller cells protruded into the subretinal space and formed multiple layers of cell bodies and processes between the retina and retinal pigment epithelium. By 14 months these subretinal Müller cell processes covered the entire detached retina, and appeared morphologically like an astroglial scar. Similar changes in human retinal detachments may significantly influence the degree of visual recovery after retinal reattachment, especially in retinae detached for more than a few days.     

Studies of experimentally induced retinal degeneration: 2. Early morphological changes produced by lipid peroxides in the albino rabbit

When pure, synthetic lipid hydroperoxides (LHP) were injected into the vitreous body of albino rabbits, electrical activity was decreased in all components of the electroretinogram (ERG) in a progressive and time-related manner. In the early phase morphological changes occurred at the interface between the photoreceptor outer segments and the retinal pigment epithelium (RPE) in response to LHP. These findings commenced within a few hours after injection and continued during the following 2-3 weeks, when the ERG was completely extinguished. Two days after injection, the rod outer segments (ROS) were swollen and damage of the RPE apical villi was observed. This initial event was followed by additional changes in the RPE which embraced swelling, accumulation of residual bodies, complete loss of ROS and enlargement and disruption of Bruch's membrane. The precursors of residual bodies appeared to result from focal, peroxidative damage to ROS discs which apparently rendered these materials undegradable by the RPE. As ROS degeneration continued, the RPE showed hypertrophy and modification. These studies provided evidence for a sequential destruction of the neural retina and RPE during oxidative damage involving lipid peroxidation. The mechanism appeared to differ from that produced by other toxic compounds or those which resulted from vitamin E or A deficiency. This new model system is thought to be useful in 1) explaining differences in susceptibility of inner ROS disks versus other membranes, 2) determining how the RPE metabolizes abnormal ROS, 3) studying RPE reactivity following trauma and/or retinal detachment, and 4) determining factors which produce degeneration of Bruch's membrane.     

猫视网膜脱离后视网膜色素上皮细胞的行为观察

目的 观察猫视网膜脱离后，视网膜色素上皮细胞(RPE)的形态学改变及行为变化。方法 28只猫利用微穿刺技术将0．25％Healon注入到视网膜下腔造成视网膜脱离。脱离0．5～90d的视网膜用3％戊二醛固定，加工成组织切片，光镜和电镜下观察RPE细胞形态学变化。结果 视网膜脱离24h，视网膜色素上皮细胞顶端突起被短而均匀的指样突起所取代，RPE细胞顶端表面开始出现耸起。随着脱离时间的延长，细胞表面的这种耸起变得更加明显。脱离14d，RPE细胞开始向视网膜下腔迁移，1～2个月后，在视网膜下腔可以观察到一些小的RPE细胞团簇。结论 视网膜脱离后，RPE细胞的形态发生迅速改变，并且依赖视网膜脱离的时间呈进行性进展。视网膜脱离能诱导RPE细胞形状发生变化，这种形状改变可能与细胞的增殖行为有关。     

Retinal pathology in the Kearns-Sayre syndrome.

Examination of the retinal tissues obtained at necropsy from a 14-year-old boy with Kearns-Sayre syndrome showed marked photoreceptor and pigment epithelial cell loss in the retinal periphery and around the optic nerve head. Electron microscopy of surviving retinal pigment epithelial (RPE) cells indicated a loss of apical microvilli and basal infoldings. The RPE was unusually devoid of melanosomes and showed no evidence of phagocytosis of photoreceptor debris. The cytoplasm of the RPE contained numerous, often enlarged, mitochondria. These structural changes suggested that a breakdown in the energy dependent interrelationships between the RPE and the photoreceptor layer was responsible for the outer retinal degeneration. The finding of numerous macrophages in the subretinal space suggests a secondary inflammatory component in the retinal degeneration.     

Mannose receptor is expressed in normal and dystrophic retinal pigment epithelium.

In normal retinas, the phagocytosis of shed photoreceptor outer segments is mediated in part through a mannose receptor protein located in the apical retinal pigment epithelium membrane. As dystrophic rats of the Royal College of Surgeons have a defect in which the retinal pigment epithelium (RPE) is unable to phagocytize the shed outer segments, it is hypothesized that mannose receptor expression will be lost with the progression of photoreceptor degeneration. Immunohistochemical and molecular techniques have been used to study the developmental expression of the mannose receptor in normal and dystrophic retinal pigment epithelium. By immunofluorescence, the mannose receptor is localized to the retinal pigment epithelium, apical membrane region, beginning around 5 days postnatally in both normal and dystrophic retinas. In immunoblots, bands at 175 kDa are labelled by an anti-mannose receptor antibody in apical membrane samples from both normal and dystrophic RPE at all developmental times sampled. RT-PCR analysis reveals that mannose receptor message is present in normal and dystrophic RPE samples at all developmental time points examined. The present study demonstrates that the expression of the mannose receptor begins prior to outer segment differentiation and the initiation of phagocytosis in both normal and dystrophic RPE. Expression of the mannose receptor continues to be unchanged during the progression of photoreceptor degeneration in the dystrophic retina.     

Retinal reattachment of the primate macula. Photoreceptor recovery after short-term detachment

The macula of the neural retina from 12 adult rhesus monkeys (Macaca mulatta) was detached from the overlying retinal pigment epithelium (RPE) by subretinal injection of a balanced salt solution. Seven days later, the two layers were reapposed by draining fluid from the vitreous cavity and replacing it with a 3:1 mixture of sulphur hexafluride gas and air. Animals were sacrificed at 1 hr, 2 days and 7 days after detachment, and at periods ranging from 3 to 14 days after reattachment. At 2-7 days prior to sacrifice, some eyes received an intravitreal injection of 3H-L-fucose. The eyes were then fixed for light and electron microscopy (EM), and tissue sections were processed for autoradiography (ARG) or immunocytochemistry. During the 7-day detachment interval, rod outer segments (ROSs) and cone outer segments (COSs) degenerated, but inner segments remained intact and the rest of the retina appeared normal. The apical RPE surface dedifferentiated during the detachment interval. At 3 days after reattachment, a regrowth of rudimentary ROSs and COSs had occurred, but the disc stacking was clearly abnormal. ROSs and COSs both showed an increase in length and a tendency to return to their normal configurations with increasing time after reattachment. ROSs and COSs regained approximately 40% of their normal lengths after a 2-week reattachment period; however, persistent outer segment abnormalities were frequently found in otherwise well regenerated areas. Autoradiographic results confirmed that new disc members were synthesized subsequent to reattachment. Newly synthesized rod disc membranes were uniformly labeled using antibodies to bovine opsin. Regenerating outer segments interdigitated with newly formed apical RPE processes, and radiolabeled phagosomes were identified within the RPE cytoplasm by 1 week after reattachment. Proliferation of the RPE cell layer was identified at some locations in all animals, and was strongly correlated with a lack of underlying outer segment regeneration. Because of the short detachment interval, and the absence of underlying pathology or trauma, the recovery process described here probably represents an example of optimum recovery after retinal reattachment.