Sensitivity of photoreceptors to elevated levels of cGMP in the human retina.
When isolated human retinas were cultured in the presence of a phosphodiesterase inhibitor or dibutyryl cyclic guanosine monophosphate (dbcGMP), degenerative changes occurred which were proportional to the concentration of drug used and the period of exposure. Low concentrations of either drug did not alter retinal morphology as compared to controls. Higher concentrations provoked vesiculation of rod inner segments and rounding up of cones. Numerous pyknotic nuclei were noted in the outer nuclear layer of those preparations. Combining IBMX and dbcGMP in the same medium destroyed virtually every rod in the specimen within 8 hr of incubation. Under those conditions, cones remained structurally intact although somewhat rounded. In all treatments, cells of the innerretinal layers maintained normal morphology. Our results suggest that elevated levels of cGMP in the human retina can alter certain metabolic processes in photoreceptors, which leads to degenerative changes and cell death uniquely in rod photoreceptors.
D000368:Aged; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000473:pathology; D012160:Retina / Q000187:drug effects*
D010726:Phosphodiesterase Inhibitors; D003995:Dibutyryl Cyclic GMP; D006152:Cyclic GMP