Faculty Bibliography

Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q transgenic mouse models of Huntington's disease (HD), DCA significantly increased survival, improved motor function, delayed loss of body weight, attenuated the development of striatal neuron atrophy, and prevented diabetes. The percentage of PDHC in the active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA ameliorated the deficit. These results provide further evidence for a role of energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic benefits in HD.

PURPOSE. To measure vitreous levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cellular adhesion molecule-1 (sVCAM-1) in the eyes of patients with retinal detachment (RD) due to proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR) and to determine whether the levels of these mediators correlated with clinical parameters of disease. METHODS. Undiluted vitreous specimens were collected from 50 eyes of 48 patients undergoing vitrectomy for traction RD due to PDR (21 specimens) and recurrent RD due to PVR (19 specimens). Control vitreous specimens were obtained from patients undergoing macular hole repair (10 specimens). The levels of sICAM-1 and sVCAM-1 were measured in each sample by specific enzyme-linked immunoadsorbent assays. RESULTS. Vitreous levels of sICAM-1 were significantly increased in vitreous specimens from both PVR (median +/- SD; 12.0 +/- 76.3 ng/ml; P < 0.01) and PDR (8.4 +/- 24.0 ng/ml; P < 0.01) when compared to vitreous from eyes with macular holes (0. 3 +/- 4.2 ng/ml). Vitreous levels of sVCAM-1 were significantly increased in both PVR (36.5 +/- 255.2 ng/ml; P < 0.001) and PDR (26. 2 +/- 93.5 ng/ml; P < 0.01) when compared to control vitreous (17.7 +/- 7.8 ng/ml). The vitreous levels of sICAM-1 were higher in cases of PDR which developed recurrent proliferative disease (P < 0.01) and recurrent RD (P = 0.01), whereas the levels of sICAM-1 in PVR and sVCAM-1 in PDR and PVR did not significantly correlate with these clinical parameters. CONCLUSIONS. Soluble forms of ICAM-1 and VCAM-1 are increased in the vitreous cavity of patients with RD due to PDR or PVR, reflecting the inflammatory nature of these conditions and suggesting a possible role for these mediators in the pathogenesis of proliferative retinal disease. The vitreous levels of these sCAMs at the time of surgery may serve as a marker of inflammation, but their specific levels do not predict the likelihood of recurrent proliferation or surgical anatomic success in most cases of PVR and PDR

PURPOSE: Retinal ischemia and neovascularization (NV) are important components of many retinal disorders. To facilitate further investigation of retinal ischemia and neovascularization, we sought to develop a reproducible in vivo experimental model of venous occlusion by photodynamic thrombosis in rats. METHODS: After anesthesia, 27 eyes of pigmented rats received an intraperitoneal injection of 0.2 ml of, 10% sodium fluorescein 15 minutes prior to laser treatment. With a blue-green argon laser, selected venous sites next to the optic nerve head were photocoagulated indirectly with a 78 diopter lens. Venous occlusion was accomplished using laser parameters of 1.0 second, 50 microns, and 50-100 mW. For a control group, 10 eyes were coagulated on the retina between major vessels using the same parameters after fluorescein injection. For a second control group, 1% sodium hyaluronate was injected into the subretinal space to make a long-standing retinal detachment in 5 eyes. RESULTS: With 1-8 laser impulses, each venous occlusion was obtained and was associated with extreme venous constriction and tortuousity. Retinal edema became evident 10-30 minutes after treatment in the sectors associated with the occluded veins. This edema became a bullous retinal detachment (RD) within 12 hours and intra-retinal hemorrhage was observed. The retinal edema continued for 3-10 days and the retinas reattached spontaneously. Prior to or after retinal reattachment 70% (19/27) of eyes developed retinal NV and tractional RD. Of these, 11 developed NV of the optic disc (NVD), 6 developed NV elsewhere (NVE), and 2 developed NVD and NVE. In 30% (8/27) of the eyes, retinal edema resolved without evidence of NV. In control groups no eyes showed either circulatory disorders or evidence of NV. CONCLUSIONS: This is a new model of retinal ischemia and associated neovascularization established by venous thrombosis that is easily reproducible. Many aspects of rat retinal physiology are known and this model has promise as an avenue for further investigation