Diabetes is a common cause of blindness in persons of working age. It has been proposed that the sequela of retinopathy in diabetic individuals is a consequence of retinal hypoxia that develops in response to increased metabolism of the inner retina. Although this hypothesis is constant with known effects of hyperglycemia and changes in pathology following treatment for proliferative retinopathy, elucidation of a mechanism for retinal hypoxia in diabetes has been difficult. The first goal of this study is to determine the relationship between progressive stages of diabetic retinopathy and oxygen utilization in the inner retina, which could produce hypoxia. For different well defined stages of retinopathy, the investigators will determine if acute hyperglycemia elevates inner retinal oxygen consumption and determine the extent to which vascular autoregulation, which would normally respond to increased oxygen demand, becomes impaired during hyperglycemia. The PI will establish whether change in retinal vessel oxygen saturation and blood flow, which are measures of autoregulatory function, are also predictive for stages of retinopathy. A mechanism by which relative hypoxia could alter distribution of capillary perfusion will be tested. The second goal is to ascertain whether the degree of photoreceptor damage resulting from panretinal photocoagulation treatment for proliferative retinopathy could be reduced by determining if retinal thinning is a significant mechanism of oxygenation. This research will employ novel imaging techniques for retinal vessel oximetry and new laser scanning technology for measuring blood flow in retinal circulations and individual capillaries.
| Cai, Jun; Qi, Xiaoping; Kociok, Norbert et al. (2012) ?-Secretase (BACE1) inhibition causes retinal pathology by vascular dysregulation and accumulation of age pigment. EMBO Mol Med 4:980-91 |
