Monoclonal antibody labels both rod and cone outer segments of turtle photoreceptors.

We have studied the immunoreactivity of turtle photoreceptors to a monoclonal antibody (MAb 15-18) which binds to the external loop connecting bovine rhodopsin helices IV-V. Three chromatic types of cone photoreceptors were identified by the presence and color of oil droplets. MAb 15-18 intensely labeled the outer segments of both rods and green cones. In addition, a weak cross-reactivity was also found in the outer segments of red cones having a pale-green oil droplet, and of blue cones. Other morphological subtypes of red cones, cones with a red oil droplet and both members of double cones, showed no labeling. Our results indicate that rhodopsin and green cone opsin have a similar antigenic determinant, and that two different structural forms of red cone opsin may be present in the turtle retina.     

Localization of iodopsin in the chick retina during in vivo and in vitro cone differentiation

Using highly specific antibodies against a chick red-sensitive cone pigment, iodopsin, we investigated the localization of iodopsin in the developing and mature chick retina. The chick retina contains several different photoreceptor types, including a rod, a double cone with a principal and accessory cone, and four different types of single cones. Immunocytochemical observations revealed that outer segments (OS) of one of the single cones (type 1) and both cells of the double cone were strongly immunoreactive to anti-iodopsin antibodies. The Golgi regions and small vesicular structures in the inner segments (IS) of these cells also were intensely stained, indicating a continuous synthesis of iodopsin and its addition to the newly formed cone OS. In the differentiating cones of the developing but immature chick retina, iodopsin immunoreactivity was found at the plasma membranes of both the IS and the terminals (pedicles). This suggests that unidirectional transport of iodopsin to the outer segment may be established during cone differentiation. Immunostaining in the outer plexiform layer (OPL) produced two bands, suggesting that the pedicles of the double cones and type 1 single cones terminate at different positions in this layer. Application of the antibodies to a cell culture system of the chick retina revealed that cells immunoreactive to anti-iodopsin differ slightly in morphology from those reactive with anti-rhodopsin. Since antibodies to iodopsin and rhodopsin stained different types of photoreceptors in the intact chick retina, it will be possible to analyze cell lineage of rods and cones in vitro by use of these antibodies.     

Morphologic identification of the OFF-type blue cone bipolar cell in the rabbit retina

PURPOSE: Bipolar cells play major roles in transmitting visual signals from photoreceptors to ganglion cells and can be subdivided into at least 10 to 13 distinct types based on their morphology and physiology. This study aimed to morphologically identify the blue cone bipolar cells responsible for transmitting color signals in the rabbit retina. METHODS: To find this cell type, bipolar cells were injected with a neuroanatomic tracer in the whole-mount rabbit retina and were subsequently labeled with peanut agglutinin and S-cone opsin to verify their cone selectivity. RESULTS: Results indicated that all narrow- and medium-field bipolar cells showed no selectivity for cone type. Among wide-field bipolar cells, one type made exclusive contact with S-cones and was identified to be a blue cone bipolar cell. This cell type gave rise to four to five branchless primary dendrites that specifically contacted S-cone pedicles and their axons ramified in sublamina a of the inner plexiform layer. CONCLUSIONS: In addition to the ON-type blue cone bipolar cell found in all mammalian retinas, the authors have identified the OFF-type blue cone bipolar cell in this study. Therefore, both ON and OFF blue cone bipolar cells are responsible for color information transmission in the rabbit retina.     

Retinal bipolar cells: temporal filtering of signals from cone photoreceptors

The temporal dynamics of the response of neurons in the outer retina were investigated by intracellular recording from cones, bipolar, and horizontal cells in the intact, light-adapted retina of the tiger salamander (Ambystoma tigrinum), with special emphasis on comparing the two major classes of bipolars cells, the ON depolarizing bipolars (Bd) and the OFF hyperpolarizing bipolars (Bh). Transfer functions were computed from impulse responses evoked by a brief light flash on a steady background of 20 cd/m(2). Phase delays ranged from about 89 ms for cones to 170 ms for Bd cells, yielding delays relative to that of cones of about 49 ms for Bh cells and 81 ms for Bd cells. The difference between Bd and Bh cells, which may be due to a delay introduced by the second messenger G-protein pathway unique to Bd cells, was further quantified by latency measurements and responses to white noise. The amplitude transfer functions of the outer retinal neurons varied with light adaptation in qualitative agreement with results for other vertebrates and human vision. The transfer functions at 20 cd/m(2) were predominantly low pass with 10-fold attenuation at about 13, 14, 9.1, and 7.7 Hz for cones, horizontal, Bh, and Bd cells, respectively. The transfer function from the cone voltage to the bipolar voltage response, as computed from the above measurements, was low pass and approximated by a cascade of three low pass RC filters ("leaky integrators"). These results for cone-->bipolar transmission are surprisingly similar to recent results for rod-->bipolar transmission in salamander slice preparations. These and other findings suggest that the rate of vesicle replenishment rather than the rate of release may be a common factor shaping synaptic signal transmission from rods and cones to bipolar cells.     

Photoreceptor distribution in the retina of adult Pacific salmon: corner cones express blue opsin

The retina of salmonid fishes has two types of cone photoreceptors: single and double cones. At the nuclear level, these cones are distributed in a square mosaic such that the double cones form the sides of the square and the single cones occupy positions at the centre and at the corners of the square. Double cones consist of two members, one having visual pigment protein maximally sensitive to green light (RH2 opsin), the other maximally sensitive to red light (LWS opsin). Single cones can have opsins maximally sensitive to ultraviolet (UV) or blue light (SWS1 and SWS2 opsins, respectively). In Pacific salmonids, all single cones express UV opsin at hatching. Around the time of yolk sac absorption, single cones start switching opsin expression from UV to blue, in an event that proceeds from the ventral to the dorsal retina. This transformation is accompanied by a loss of single corner cones such that the large juvenile shows corner cones and UV opsin expression in the dorsal retina only. Previous research has shown that adult Pacific salmon have corner cones over large areas of retina suggesting that these cones may be regenerated and that they may express UV opsin. Here we used in-situ hybridization with cRNA probes and RT-PCR to show that: (1) all single cones in non-growth zone areas of the retina express blue opsin and (2) double cone opsin expression alternates around the square mosaic unit. Our results indicate that single cone driven UV sensitivity in adult salmon must emanate from stimulation of growth zone areas.     

Molecular cloning and characterization of five opsin genes from the marine flatfish Atlantic halibut (Hippoglossus hippoglossus)

Most molecular studies on the visual system in fish have been performed on freshwater teleosts such as goldfish and zebrafish where cones and rods appear simultaneously. Many marine fishes have long larval phase in the upper pelagic zone before transformation into a juvenile and a benthic life style. The retina at the larval stages consists of only single cone cells; later during metamorphosis double cones and rods develop. The flatfish Atlantic halibut (Hippoglossus hippoglossus) is a typical example of a marine species with such a two-step retina development. In this study, we have cloned five different opsins from Atlantic halibut larvae and juvenile retinas. Sequence comparisons with other opsins and phylogenetic analysis show that the five genes belong to the opsins of long-wavelength sensitive (L); middle-wavelength sensitive, M(Cone) and M(Rod); and short-wavelength sensitive, S(Blue) and S(Ultraviolet), respectively. In situ hybridization analysis reveals expression in double cone (L and M(Cone)), single cone (S(Blue) and S(Ultraviolet)), and rod (M(Rod)) types of photoreceptor cells in juvenile halibut retina. The visual system in Atlantic halibut seems therefore to have all four types of cone photoreceptors in addition to rod photoreceptors. This work shows for the first time molecular isolation of a complete set of retinal visual pigment genes from a marine teleost and describes the first cloning of an ultraviolet-sensitive opsin type from a marine teleost.     

Late stages of visual pigment photolysis in situ: cones vs. rods

Slow photolysis reactions and the regeneration of the dark pigment constitute the mechanisms of dark adaptation whereby photoreceptor cells restore their sensitivity after bright illumination. We present data on the kinetics of the late stages of the photolysis of the visual pigment in intact rods and red- and green-sensitive cones of the goldfish retina. Measurements were made on single photoreceptors by means of a fast-scanning dichroic microspectrophotometer. We show that in cones the hydrolysis of the opsin-all-trans 3-dehydroretinal linkage proceeds with a half-time of approximately 5s at 20 degrees C that is almost two orders of magnitude faster than in rods. 3-Dehydroretinol in cones is produced approximately 3-fold faster than retinol in amphibian rhodopsin rods; the rate of the reaction is limited by the speed of retinal reduction catalyzed by retinoldehydrogenase. The fast hydrolysis of the 3-dehydroretinal/opsin Schiff base and the correspondingly fast appearance of the substrates for dark visual pigment regeneration (free opsin and 3-dehydroretinol) provide essential conditions for faster dark adaptation of cone (diurnal) as compared to rod (nocturnal) vision.     

The ability of hyperoxia to limit the effects of experimental detachment in cone-dominated retina.

PURPOSE: To determine the ability of oxygen supplementation to ameliorate the effects of retinal detachment in a cone-dominated retina. METHODS: Retinal detachments were created in the right eyes of ground squirrels and the animals immediately placed in normoxic (room air) or hyperoxic (70% oxygen) conditions for 3 days. The retinas were sampled from different regions and investigated morphologically or immunocytochemically by light or confocal microscopy. Agarose embedded sections were immunostained with antibody probes to cytochrome oxidase, synaptophysin, medium-to-long wavelength-sensitive (M/L) cone opsin, rod opsin, excitatory amino acid transporter 1 (EAAT1), glutamate synthetase (GS), cellular retinaldehyde-binding protein (CRALBP), and peanut agglutinin (PNA) lectin. Retinal wholemounts were labeled with PNA and antibodies to short (S)-wavelength-sensitive cone opsin and rod opsin. Cell death was examined using a TUNEL assay on agarose sections or using toluidine blue staining on semithin sections. RESULTS: The percentage of dying cells relative to the total nuclei in the photoreceptor layer was significantly reduced, and the total number of nuclei was greater in hyperoxic animals. Triple labeling using TUNEL, anti-M/L cone opsin and anti-rod opsin showed that hyperoxia had a remarkable effect both on the reduction of cone cell death and the maintenance of the overall structure of cone photoreceptors. Analysis of the retinal wholemounts demonstrated the preservation of PNA, S-cone, and rod opsin antibody labeling in the detachments maintained in hyperoxic conditions. Although the disruption of cytochrome oxidase and synaptophysin was seen in normoxic animals, there was minimal disruption in hyperoxic animals. Labeling with anti-EAAT1, anti-GS, and anti-CRALBP was increased in the Müller cells of normoxic animals with detachments, but was decreased in the hyperoxic animals. CONCLUSIONS: Hyperoxia prevents the degeneration of both rods and cones in retinas heavily dominated by cones and mitigates the effect of detachment on Müller cell reactivity. The current results suggest that the rescue of cones is not secondary to that of rods.     

Immunoelectron microscopic localization of photoreceptor-specific markers in the monkey retina

Antibodies for several molecules that function in the visual process were used to localize these molecules in primate rod and cone cells. These antibodies (monoclonal or polyclonal) were prepared against Interphotoreceptor Retinoid-binding Protein (IRBP), S-antigen (S-Ag), opsin, alpha-transducin and also against cyclic GMP (cGMP). Lowicryl-embedded tissues were labeled with secondary antibodies linked to colloidal gold. Although IRBP is predominantly an extracellular protein, the relatively small amount found intracellularly was localized mainly in rods, with little in cones. Opsin, S-Ag and cGMP were found mainly in rod cell outer segments. A polyclonal antiserum raised against transducin-alpha purified from rod outer segments predominantly labeled rod cells, but an antiserum against the carboxyterminal decapeptide of transducin-alpha labeled both rod and cone cells. Thus, most of these specialized molecules are present predominantly in rod cells, confirming major differences in components of the visual cycle in rods and cones.     

Lateral interactions in the outer retina

Lateral interactions in the outer retina, particularly negative feedback from horizontal cells to cones and direct feed-forward input from horizontal cells to bipolar cells, play a number of important roles in early visual processing, such as generating center-surround receptive fields that enhance spatial discrimination. These circuits may also contribute to post-receptoral light adaptation and the generation of color opponency. In this review, we examine the contributions of horizontal cell feedback and feed-forward pathways to early visual processing. We begin by reviewing the properties of bipolar cell receptive fields, especially with respect to modulation of the bipolar receptive field surround by the ambient light level and to the contribution of horizontal cells to the surround. We then review evidence for and against three proposed mechanisms for negative feedback from horizontal cells to cones: 1) GABA release by horizontal cells, 2) ephaptic modulation of the cone pedicle membrane potential generated by currents flowing through hemigap junctions in horizontal cell dendrites, and 3) modulation of cone calcium currents (I(Ca)) by changes in synaptic cleft proton levels. We also consider evidence for the presence of direct horizontal cell feed-forward input to bipolar cells and discuss a possible role for GABA at this synapse. We summarize proposed functions of horizontal cell feedback and feed-forward pathways. Finally, we examine the mechanisms and functions of two other forms of lateral interaction in the outer retina: negative feedback from horizontal cells to rods and positive feedback from horizontal cells to cones.     

AMPA-selective glutamate receptor subunits GluR2 and GluR4 in the cat retina: an immunocytochemical study

AMPA-selective glutamate receptors play a major role in glutamatergic neurotransmission in the retina and are expressed in a variety of neuronal subpopulations. In the present study, immunocytochemical techniques were used to visualize the distribution of GluR2 and GluR4 subunits in the cat retina. Results were compared with previous localizations of GluR1 and GluR2/3. Staining for GluR2 was limited to a small number of amacrine and ganglion cells whereas GluR4 staining was present in A-type horizontal cells, many amacrine cells including type AII amacrine cells, and the majority of the cells in the ganglion cell layer. Analysis of synaptic relationships in the outer plexiform layer showed the GluR4 subunit to be concentrated at the contacts of cone photoreceptors with A-horizontal cells. In the inner plexiform layer, both GluR2 and GluR4 were postsynaptic to cone bipolar cells at dyad contacts although GluR2 staining was limited to one of the postsynaptic elements whereas GluR4 immunoreactivity was often seen in both postsynaptic elements. Unlike GluR2, GluR4 was also postsynaptic to rod bipolar cells where it could be visualized in processes of AII amacrine cells. The data indicate that GluR3 and GluR4 subunits are colocalized in a number of cell types including A-type horizontal cells, AII amacrine cells, and alpha ganglion cells, but whether they are combined in the same multimeric receptors remains to be determined.     

Preservation of outer retina and its synaptic connectivity following subretinal injections of human RPE cells in the Royal College of Surgeons rat

We have examined how transplantation of an RPE cell line to the subretinal space of RCS rats affects the distribution of synaptic connectivity markers in the outer plexiform layer of the retina. Using markers of pre- and post-synaptic profiles (bassoon and synaptophysin as presynaptic markers and mGluR6 for postsynaptic profiles) we found that the normal orderly patterns seen between photoreceptors and rod and ON-cone bipolar cells were severely disrupted in dystrophic rats. In areas in which injected cells preserved photoreceptors, more normally appearing pairing of pre- and post-synaptic markers was seen for both rods and cones. The degree of normality correlated with the amount of photoreceptor rescue. The secondary changes that are normally seen in bipolar and horizontal cells were prevented by the photoreceptor preservation. ERG recordings in the animals subsequently studied morphologically showed that both a- and b-waves could be rescued by grafting, albeit with lower amplitudes than normal. Together these anatomical and physiological studies indicate that besides the integrity of outer nuclear layer cells and phototransduction processes, relay circuitry through the outer retina was rescued by cell grafts.     

Localization of AMPA-selective glutamate receptor subunits in the cat retina: a light- and electron-microscopic study

The distribution of AMPA-selective glutamate receptor subunits was studied in the cat retina using antisera against GluR1 and GluR2/3. Both antisera were localized in postsynaptic sites in the outer plexiform layer (OPL) as well as the inner plexiform layer (IPL). Immunoreactivity for GluR1 was seen in a subpopulation of OFF cone bipolar cells and a number of amacrine and ganglion cells. Within the IPL, processes staining for GluR1 received input from OFF and ON cone bipolar cells but not from rod bipolars. Labeling for GluR2/3 was seen in horizontal cells, an occasional cone bipolar cell, and numerous amacrine and ganglion cells. In the IPL, GluR2/3 staining was postsynaptic to cone bipolar cells in both sublaminae. AII amacrine cells which receive rod bipolar input were also labeled for GluR2/3. With both antisera, staining was limited to a single member of the bipolar dyad complex, providing morphological evidence for functional diversity in glutamatergic pathways.     

Immunocytochemical reactivity of rod and cone visual pigments in the sturgeon retina.

Microspectrophotometry and immunocytochemistry with several antivisual pigment antibodies were used to study visual cells of the Siberian sturgeon, Acipenser baeri Brandt. The retina contained rods and three morphological types of cones: large cones with oil drops, small cones with oil drops, and cone-like cells without oil drops. Rods and cone-like drop-free cells were found to possess porphyropsin-549, while the large oil drop-bearing cones contained red-sensitive (P613), green-sensitive (P542), and blue-sensitive (P462) visual pigments. The immunocytochemical staining pattern with three antibodies to visual pigment proteins also revealed one visual pigment in rods and three visual pigments in cones. Rods were labeled with all three antibodies, while the majority of large cones (type I), presumably the red-sensitive ones, were negative with the polyclonal serum AO against bovine opsin. A less-frequently occurring large cone type (type II) was stained by all three antibodies including mAb COS-1 specific to middle-to-long-wave visual pigments in birds and mammals, and is thought to be green-sensitive. An even less-frequent large cone type (type III, probably the blue-sensitive one) did not bind COS-1. The small cones with oil droplets showed immunoreactivities similar to either type II or type III cones. The oil drop-free small photoreceptor exhibited a staining pattern identical with that of rods. These results indicate that the immunocytochemical approach can be used to reveal photoreceptor-specific neural connections in the sturgeon retina.     

Two types of lamprey retina photoreceptors immunoreactive to rod- or cone-specific antibodies

The localization of structures immunoreactive to antisera against opsin (OPS; a specific marker for rods) and against visinin (VIS; a specific marker for cones in the vertebrate retina) was investigated in the retina of the river lamprey (Lampetra japonica) by means of fluorescence microscopy. Different immunoreactive structures were found with the two antisera. A vitreadly located structure in the outer nuclear layer displayed OPS-like immunoreactivity, while a scleradly located one exhibited VIS-like reactivity. Thus, the two antisera applied to the retina of the river lamprey permit the distinguishing of rod and cone immunoreactive photoreceptors such as occurs typically in all vertebrate classes. The former appears in the outer segments of a type of rod cells, and the latter in the cell bodies and axons of cones.     

Expression of CNTF receptor-alpha in chick violet-sensitive cones with unique morphologic properties

PURPOSE: Application of ciliary neurotrophic factor (CNTF) can rescue mature photoreceptors from lesion-induced and hereditary degeneration. In the chick retina, expression of the CNTF receptor is present in a subpopulation of photoreceptor cells. The present study was undertaken to identify the CNTF receptor-expressing photoreceptors and to describe the subcellular localization of the receptor protein. METHODS: The localization of the CNTF receptor was analyzed by light and electron microscopic immunocytochemistry in chick retinal wholemount preparations, with an antibody for CNTF receptor alpha (CNTFRalpha). Immunoreactive cells were identified by double labeling with immunocytochemical markers for photoreceptor subpopulations. RESULTS: The CNTFRalpha antibody labeled evenly distributed outer segments (OS) of a photoreceptor subpopulation. CNTFRalpha-positive OS were associated with oil droplets of uniform size. Receptor immunoreactivity did not colocalize with markers for rods and red-green cones. Complete overlap was found after double labeling with the antibody CERN 933, which recognizes violet-sensitive cones in the chick retina. Ultrastructurally, the CNTFRalpha-immunoreactive OS showed rodlike properties: an elongated shape and stacks of membrane discs separated from the plasma membrane. Immunoreactivity was completely restricted to the plasma membrane of the OS and the inner membrane sheet of the photoreceptor calices present in avian retinas. CONCLUSIONS: CNTFRalpha expression identifies a unique type of photoreceptors in the avian retina which does not fit into the classic morphologic definition of rods and cones. The specific expression in violet-sensitive photoreceptors suggests that CNTF may have a neuroprotective role related to the specific function of these cells.     

Localization of ionotropic glutamate receptors to invaginating dendrites at the cone synapse in primate retina

The separation of OFF pathways that signal light decrements from ON pathways that signal light increments occurs at the first retinal synapse. The dendrites of OFF bipolar cells abut the cone pedicle at basal positions distal to the site of glutamate release and express ligand-gated or ionotropic glutamate receptors (GluR). The dendrites of ON bipolar cells penetrate narrow invaginations of the cone pedicle proximal to the site of release and express the G-protein-coupled, metabotropic glutamate receptor, mGluR6. However, recent studies demonstrating the expression of GluR subunits in the rodent rod bipolar cell, known to yield an ON response to light, call this basic segregation of receptors into question. The light-microscopic distribution of many glutamate receptors in the primate retina is now well established. We reexamined their ultrastructural localization in the outer retina of Macaca fascicularis to test systematically whether invaginating dendrites at the cone synapse, presumably from ON bipolar cells, also express one or more ionotropic subunits. Using preembedding immunocytochemistry for electron microscopy, we quantified the distribution of the AMPA-sensitive subunits GluR2/3 and GluR4 and of the kainate-sensitive subunits GluR6/7 across 207 labeled dendrites occupying specific morphological loci at the cone pedicle. We report, in agreement with published investigations, that the majority of labeled processes for GluR2/3 (70%) and GluR4 (67%) either occupy basal positions or arise from horizontal cells. For GluR6/7, we find a significantly lower fraction of labeled processes at these positions (47%). We also find a considerable number of labeled dendrites for GluR2/3 (10%), GluR4 (21%), and GluR6/7 (18%) at invaginating positions. Surprisingly, for each subunit, the remainder of labeled processes corresponds to "fingers" of presynaptic cytoplasm within the cone invagination.     

The topographical distribution of rods and cones in the adult chicken retina

The relative proportion of rods and cones (single and double) in the chicken retina was determined by counting these elements in each of nine pre-determined segments prepared as periodic acid-Schiff serial sections for rod (hyperboloid glycogen) and double cone (accessory cone paraboloid glycogen) identifications and as unfixed, flat preparations for cone determinations (colored oil droplets). Periodic acid-Schiff preparations revealed that rods and accessory cones were equal in number in all retinal segments except those located directly posterior to the posterior extremity of the pecten where the double cones out-numbered the rods in a ratio of 14 : 10. On the basis of oil-droplet pigmentation, double cones housing a golden-yellow droplet in their chief component and a small yellowish-green droplet in their accessory members were constantly observed to be twice as numerous as single cones (red droplet) in all retinal segments. These data reveal that the proportion of rods to double and single cones is 2 : 2 : 1, respectively, in all areas of the chicken retina except a posterior (lateral) segment where the ratio is 10 : 14 : 7. This area of greater cone concentration corresponds to the site of the temporal fovea of some birds and may represent the area of most acute vision in the fovea-free chicken retina.     

Glial remodeling and neural plasticity in human retinal detachment with proliferative vitreoretinopathy

PURPOSE: To investigate glial remodeling and neuronal plasticity in adult human retinal detachment complicated by proliferative vitreoretinopathy (PVR) and to grade pathologic changes with a severity scoring system. METHODS: Sixteen full-thickness retinectomy specimens obtained at retinal relaxing surgery for PVR were fixed in 4% paraformaldehyde immediately after excision and compared to similarly processed normal donor retinas. Agarose-embedded sections (100-microm-thick) were double labeled for immunohistochemistry by confocal microscopy, with antibodies against rod opsin and GFAP; vimentin and M/L-cone opsin; calbindin D and S-cone opsin; and cytochrome oxidase and synaptophysin. These staining patterns formed the basis of a retinal pathology scoring system, and immunohistochemistry was also used to detect CD68, neurofilaments, protein kinase C, growth-associated protein-43, and a pan-cone-specific enzymatic marker. Morphology was also assessed by light microscopy of resin-embedded semithin sections. RESULTS: Prolonged detachment was characterized by photoreceptor degeneration and intracellular redistribution of opsin proteins to the plasma membrane in the outer nuclear layer (ONL). Remodeling of rod synaptic terminals was characterized by terminal retraction and also by axon extension to the inner retina in most specimens. Rod bipolar cell dendrites extended into the ONL, as did fine, horizontal cell processes. Large ganglion cells showed upregulated neurofilament and GAP-43 expression, with neurites sprouting from somata and axon collaterals. Anti-cytochrome oxidase labeling of surviving inner segments was reduced but detectable in all specimens, as was anti-calbindin D labeling of horizontal and amacrine cells. All specimens demonstrated a marked upregulation of Muller cell and astrocyte expression of GFAP and vimentin. More severe degenerative changes correlated with trauma and prolonged detachment duration when scored according to this system. CONCLUSIONS: The neural and glial components of detached neurosensory retina complicated by PVR exhibit pathology that changes characteristically with increasing detachment severity. Even in advanced degeneration, most of the structural motifs necessary for functional recovery are retained. Evidence of remodeling in the first-, second-, and third-order neurons of detached adult human retina may represent an attempt to re-establish synaptic connectivity.