Loss of cone molecular markers in rhodopsin-mutant human retinas with retinitis pigmentosa

PURPOSE: To examine the effect of rhodopsin mutations on cone photoreceptor s in human retinas with retinitis pigmentosa (RP). METHODS: Four RP retinas with rhodopsin mutations and four normal retinas w ere examined by immunofluorescence with a battery of cell-specific antibodi es against cone and rod cytoplasmic and outer segment membrane proteins. Ar eas of the retinas were studied that showed maximal preservation of photore ceptor structure. RESULTS: All four RP retinas showed loss of rods, ranging from mild (T-17-M ), to more severe (P-23-H), to advanced degeneration (Q-64-ter and G-106-R) . The majority of cones in the T-17-M and P-23-H retinas were cytologically normal but showed loss of immunoreactivity for the cytoplasmic proteins 7G 6, calbindin, and X-arrestin. The cone outer segments (OS) remained positiv e for cone opsins and peripherin-2 (rds/peripherin). All remaining cones in the Q-64-ter and G-106-R retinas were degenerate, with short to absent OS, but had strong reactivity for these cytoplasmic and OS membrane markers. C ones in the maculas of the RP retinas were degenerate, with short to absent OS, but retained strong labeling for the cytoplasmic and OS proteins. CONCLUSIONS: Even before cones show cytologic changes in response to rod ce ll degeneration, they lose immunoreactivity for certain cytoplasmic protein s. These cones later show shortening and loss of OS, although their OS memb rane proteins remain well labeled. Cones may down regulate expression of bo th cytoplasmic and outer segment membrane proteins in response to mutant ro d cell dysfunction and/or cell death in human RP retinas. Such cytologic an d immunocytochemical changes in the cones may presage death of these critic al cells in the later stages of RP.