RENIN-CONTAINING MULLER CELLS OF THE RETINA DISPLAY ENDOCRINE FEATURES

Purpose. An ocular renin-angiotensin system has been implicated in the proliferation of retinal brood vessels and blindness in diabetes mell itus. Its cellular basis has not been established. The objective was t o identify sites of renin synthesis, secretion, and processing in eyes from humans, BALB/c mice, Sprague-Dawley rats, and a hypertensive tra nsgenic rat model (mREN-2) that displays amplified extrarenal renin sy nthesis. Methods. Paraffin sections of eyes were incubated with antise ra to renin protein, prorenin, vimentin, and Muller cells. Enzyme kine tic renin assay was performed on extracts of whole eyes (excluding len s and vitreous) and comparisons made with adrenal glands and kidneys. For detection of renin mRNA, retinas were separately pooled from BALB/ c and Swiss mice. Results. In normal rodent and autopsy human eyes, la beling for renin, vimentin, and Muller cell protein was observed in th e cytoplasm of all macroglial Muller cells, with renin labeling most o bvious in endfeet closely apposed to retinal blood vessels. Prorenin l abeling was not detected. Less intense renin labeling, again without p rorenin, was seen in nonpigmented ciliary epithelium of rodents. In tr ansgenic (mREN-2) rat eyes, renin and prorenin labeling of Muller cell s and nonpigmented ciliary epithelium were intense. Prorenin was local ized to the posterior region of Muller cells but only sparsely to endf eet in rodent retinas, and renin was present only in an active form in amounts one third that of one adrenal. Renin mRNA was readily detecte d. In human retina, renin was present in active and pro-forms, and the total amount was approximately one fiftieth that of adrenal. Conclusi on. Renin is synthesized in the retina and is specifically localized t o the macroglial Muller cells. Nonpigmented ciliary epithelium also co ntains renin. The presence of prorenin in the posterior part of the Mu ller cell, with active renin throughout but notably in endfeet in appo sition to retinal capillaries, suggests directional processing of reni n. These findings are consistent with earlier suggestions that retinal neovascularization may be associated with Muller cell dysfunction.