Nitric oxide and form-deprivation myopia.

摘要

Deprivation of form-vision induces myopia, characterized by a negative refractive error and ocular enlargement. Fujikado et al. (1997) proposed that nitric oxide, produced in retinal cells, causes form-deprivation myopia (FDM) in chicks. Work in our lab raises questions about the validity that study's results. Therefore, the effects of NO donors/inhibitors on FDM and normal ocular development were further tested.; Chick eyes were goggled or remained open, and injected with SNP (NO donor), L-NAME, L-NMMA or L-NIO (NOS inhibitors) and later refracted, measured and weighed. Histological and immunocytochemical techniques were used to assess retinal condition. Nitrate and nitrite levels were measured in retina and RPE of eyes treated with L-NIO to determine whether NO production was inhibited. Some eyes were treated with SNP and IBMX, later sectioned and labelled with antibodies raised to cGMP to resolve whether SNP treatment resulted in increased NO availability within the retina.; 10 nmol SNP stimulated cGMP production in amacrine and bipolar cells with no effect on development. In goggled eyes, 100 nmol SNP reduced ocular size and myopic refraction while damaging photoreceptors (mainly rods), causing swelling, disorganization, shortening and thinning of rod outer segments accompanied by potential autophagy and DNA fragmentation in the photoreceptor layer. No other retinal cell type appeared to be damaged. 1000 nmol SNP retarded ocular growth and destroyed the retina, leaving a pigmented scar. While L-NAME prevented FDM inconsistently at 16--20 mumol, it had no effect at lower doses. Other inhibitors showed no effect, despite suppressing NO levels.; At sub-toxic doses, SNP and NOS-inhibitors did not affect normal ocular development or FDM. Therefore, NO does not appear to regulate normal ocular growth or myopiagenesis. High doses of NO are retinotoxic, and the associated effect on photoreceptors/RPE and eye growth is consistent with previous reports that normal or myopic growth requires intact photoreceptors.