[Role of nitric oxide in apoptosis of retinal neurons in human fetuses]

The localization of NADPH-diaphorase (NADPH-d), inducible NO-synthase (iNOS) and TUNEL-immunoreactive neurons was studied in the retina of human fetuses in the I-III trimesters of pregnancy. High NADPH-d activity was found in internal segments of photosensory cells, amacrine and ganglion cells. The population of NADPH-d-positive amacrine cells included three types of neurons. Neurons of the 1st type had large size and scarce dendritic field, occupying the inner nuclear and outer plexiform layers. Small neurons of the 2nd type were located in the inner plexiform layer. Ectopic amacrine cells of 3rd type could be found in the outer part of the ganglion cell layer. High density of the NADPH-d-positive neurons was detected in the central portion of retina surrounding fovea centralis and the optic disk area. The activity of NADPH-d was found to grow progressively in ontogenesis and to correlate with the appearance of immunoreactive iNOS in neurons. Immunoreactive iNOS marked a subpopulation of amacrine and ganglion cells which appeared in weeks 20-21 of gestation and attained maximal immunoreactivity by the end of the III trimester. TUNEL-immunoreactive nuclei of the neurons with the signs of the apoptotic destruction were found in weeks 30-31 of gestation. The highest apoptotic index was found in the population of ganglion cells. The data obtained strongly suggest that NO is a factor, mediating the neuronal apoptosis during the critical period of a differentiation of interneuronal connections in the human retina.