Program list

SYMPOSIUM: FUNDAMENTALS
Moderators: Khaled El-Rakhawy, Cesare Forlini
Sunday, September 14th, 2003 ; 8:15 - 12:35

EFFECT OF TRAUMA AND RETINAL DETACHMENT WITH PVR ON RETINAL CELL BIOLOGY
Charanjit Sethi
London, United Kingdom

Purpose: To investigate glial remodeling and neuronal plasticity in adult human retinal detachment complicated by proliferative vitreoretinopathy (PVR) and to grade pathological 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 retina. One hundred micrometre thick agarose-embedded sections were double labelled for immunohistochemistry by confocal microscopy using antibodies against: rod opsin and GFAP; vimentin and M/L cone opsin; calbindin D and S cone opsin; cytochrome oxidase and synaptophysin. These staining patterns formed the basis of a retinal pathology scoring system, and immunohistochemistry was also employed 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 semi-thin sections.
Results: Prolonged detachment was characterised 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 characterised by terminal retraction and also 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 upregulated neurofilament and GAP-43 expression with neurite sprouting from somata and axon collaterals. Anti-cytochrome oxidase labelling of surviving inner segments was reduced but detectable in all specimens, as was anti-calbindin D labelling of horizontal and amacrine cells. All specimens demonstrated a marked upregulation of Müller cell and astrocyte expression of GFAP and vimentin. More severe degenerative changes correlated with trauma and prolonged detachment duration when scored according to our system.
Conclusion: 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.