Identification of ganglion cell neurites in human sub - and epiretinal membranes

Aims: To determine if neural elements are present in sub-and epiretinal PVR membranes as well as in diabetic, fibrovascular membranes removed from patients during vitrectomy surgery. Methods: Human sub-and epiretinal membranes of varying durations were immunolabeled with different combinations of antibodies to GFAP, vimentin, neurofilament protein and laminin. Results: Anti-neurofilament labeled neurites from presumptive ganglion cells were frequently found in epiretinal membranes and occasionally found in subretinal membranes. In addition the neurites were only observed in regions that also contained glial processes. Conclusions: These data demonstrate that neuronal processes are commonly found in human peri-retinal cellular membranes similar to what has been demonstrated in animal models. These data also suggest that glial cells growing out of the neural retina form a permissive substrate for neurite growth and thus may hold clues to factors that support this growth. 3 INTRODUCTION Injury to CNS tissue often stimulates the activation of glial cells, ultimately resulting in their proliferation and hypertrophy throughout the damaged region.[1, 2] One consequence of this gliosis can be impaired regeneration of neurons as their processes are unable to migrate through the damaged area to reestablish synaptic connections. The newly formed glial " scar " acts not only as a physical barrier to regeneration but also contains inhibitory molecules for neuronal growth.[3] Retinal detachment, which separates the neural retina from the retinal pigment epithelium (RPE), initiates a similar reaction from the radial glial cells of the retina, the Müller cells.[4] Within 3 days after detachment, many Müller cells are undergoing cell division and hypertrophy within the retina.[5, 6] Also at this time, a subpopulation of these cells begin to grow out of the retina into the newly created " subretinal space " resulting in subretinal fibrosis.[7, 8] Ultimately these cells form large subretinal glial " membranes " or scars on the surface of photoreceptors that can impede the regeneration of photoreceptor outer segments following retinal reattachment. [9] While retinal reattachment appears to halt the growth of the Müller cells into the subretinal space, in some cases Müller cells redirect their growth into the vitreous cavity and form " epiretinal " membranes [10] in a condition termed proliferative vitreoretinopathy (PVR). PVR is the most common cause of failure of retinal reattachment surgery, as cells that have attached to the inner limiting membrane contract and cause a re-detachment of the retina. The cellular composition of these epiretinal membranes has been shown to …