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ACKNOWLEDGMENTS This work was supported by in part by grant RP-140-000-038-112 to M.-L.G. ; , the Thailand Research Fund to P.W. ; , the National Institutes of Health grants AI 35800 and RR 01081 to P.J.R. ; , and the Australian National Health and Medical Research Council grants to K.J.S. and K.K. ; . M.L. gratefully acknowledges National University of Singapore for a graduate scholarship. We thank Belinda J. Lee and Jiri Gut for expert technical assistance with the falcipain 2 assays and Wu Xiang for carrying out the MTT assays, because endep uses.

IOVS, March 2005, Vol. 46, No. 3 rats had slightly lower levels of retinal ACE than did SD rats. This was most notable at P7 and P90. The reason for this strain difference is probably the overexpression of the retinal RAS in Ren-2 rats, which has the effect of suppressing tissue ACE levels. Our previous studies support this finding, as adult Ren-2 rats have reduced levels of plasma ACE compared with SD rats.47 It should be noted that in several species, ACE increases over the perinatal period in lung, kidneys, heart, and aorta.46, 48, 49 The reason for the increase in ACE with tissue development is not precisely known, but could relate to the extent of vascularization. For instance, it has been suggested that the postnatal increase in pulmonary ACE expression in lambs may partly reflect the increase in capillary surface area associated with growth.50 In the present study, RAS components were localized to cells in the GCL, which could represent ganglion and displaced amacrine cells.51 RAS components also exist in macroglial Muller cells.6 Together, these findings suggests that the angio tensin produced in these cells exerts a paracrine effect on the neighboring vasculature. Indeed, neurons and glia in the retina are structurally aligned with the retinal vasculature, 52 and contribute to the epiretinal membranes that form in diabetic retinopathy.53 Alternatively, the retinal RAS may influence neuronal activity reviewed in Ref. 54 ; . Of interest is that blockade of RAS modulates the a- and b-waves of the electroretinogram.25 ACE may also have a role in neuronal development in the retina. In chicken retina that lack blood vessels, ACE activity and gene expression increase in the developing embryo retina and peak transiently postpartum.55, 56 This developmental upregulation of ACE coincides with the period of synaptogenesis in the chicken retina, leading to the suggestion that ACE may be involved in the fine tuning of the neuronal retinal network and or the metabolism of neuropeptides, such as substance P.

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