Ocular structure and function in an aged monkey with spontaneous diabetes mellitus

Diabetes mellitus develops spontaneously in middle-aged, obese rhesus monkeys, thus making them a good model for examining the effects of co-morbid factors on the development of end-organ damage. Changes in structure and function in the eyes of one monkey who spontaneously developed type 2 diabetes are reported here. This animal had concomitant hypertension, high levels of triglycerides and serum cholesterol, and a low fraction of high-density lipoprotein. The eyes showed intraretinal hemorrhages and large areas of retinal capillary nonperfusion. Indo-cyanin green (ICG) angiography revealed a large area of non- or poorly perfused choriocapillaris in one eye, and immunohistochemistry showed loss of viable choriocapillaries in this region. Both basal laminar deposits and hard drusen were present on areas of Bruch's membrane adjacent to nonviable choriocapillaris. Blood flow via the nasal posterior ciliary arteries to this section of choroid was not detectable by color duplex Doppler ultrasound, indicating contribution of extraocular vascular disease to ischemia in this eye. There was a severe decline in number of photoreceptor inner and outer segments, and corresponding reductions in the multifocal electroretinogram (ERG), in the areas of choriocapillaris loss. The ganzfeld ERG indicated loss in both inner and outer retinal function. Much of the ganglion cell layer was absent throughout the retina, possibly reflecting the effect of diabetes as well as chronic open angle glaucoma; the latter diagnosis supported by elevated intraocular pressures and excavated optic disks. In summary, high resolution, enzyme histochemical and histopathological analyses of a diabetic hypertensive monkey retina and choroid after serial functional in vivo analyses have demonstrated the relationship between vascular dysfunction and visual function loss. Choroidal vascular dysfunction in both large and small vessels was associated with age-related macular degeneration-like changes in Bruch's membrane and photoreceptor degeneration.