High-titer collapsin response-mediating protein-associated (CRMP-5) paraneoplastic optic neuropathy and Vitritis as the only clinical manifestations in a patient with small cell lung carcinoma.

Paraneoplastic optic neuropathy (PON) is a rare syndrome usually associated with small cell lung carcinoma. In the 27 rigorously reported cases, neurologic manifestations other than visual loss have been present in all but 2. In the single case in which vision improved in response to treatment of the cancer, the collapsin response-mediating protein (CRMP)-5 titer did not change, and the ophthalmic examination was not detailed. We describe a patient with optic neuropathy and vitritis as the only clinical manifestations of PON marked by an extremely high titer of CRMP-5 antibody. Treatment of the underlying small cell lung cancer coincided with resolution of the visual abnormalities and a dramatic decrease in the CRMP-5 titer.

Increased vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGFbeta) in experimental autoimmune uveoretinitis: upregulation of VEGF without neovascularization.

Experimental autoimmune uveoretinitis (EAU) was induced in Lewis rats and B10.A mice by immunization with S-antigen (S-Ag) to study the potential roles of vascular endothelial growth factor (VEGF) and the beta1 and beta2 isoforms of transforming growth factor (TGFbeta1 and TGFbeta2) during the progression of the disease. VEGF has been implicated as an angiogenic factor in ischemic retinopathies; however, Lewis rats developing EAU have high levels of VEGF in the retina, but no neovascularization. In the present study, immunohistochemical staining for VEGF, TGFbeta1 and TGFbeta2 was performed on the retinas of Lewis rats developing EAU or with oxygen-induced ischemic retinopathy. In rats immunized with S-antigen, a marked upregulation of VEGF was immunohistochemically visualized from the inner nuclear layer to the inner limiting membrane prior to blood-retinal barrier (BRB) failure and lymphocytic infiltration. VEGF is normally induced by hypoxia and its induction leads to neovascularization. Coincident with the increase in VEGF, there was increased immunoreactivity for TGFbeta1 and TGFbeta2 within the same layers of the retina. In contrast, rats with ischemic retinopathy and retinal neovascularization showed only a modest increase in VEGF immunoreactivity, which is largely confined to retinal ganglion cells and inner retinal vessels, and little or no increase in TGFbeta1 or TGFbeta2. In addition, in mice developing EAU, which does not have an abrupt onset as it does in rats and may involve neovascularization, a comparable upregulation of VEGF in the inner retina to that seen in rats developing EAU occurs with no increase in TGFbeta1 or TGFbeta2. Since TGFbeta can inhibit endothelial cell proliferation, it is likely that an increase in TGFbeta may prevent VEGF from exerting its endothelial growth activity in the rat EAU model, but VEGF may be operative in inducing BRB failure. These data suggest that there is a complex interaction among growth factors in the retina and that retinal neovascularization may require an imbalance between stimulatory and inhibitory factors.

Leukocyte-endothelial cell interactions in diabetic retina after transient retinal ischemia.

Diabetes is associated with increased neural damage after transient cerebral ischemia. Recently, leukocytes, which are thought to play a central role in ischemia-reperfusion injury, have been suggested to be involved in exacerbated damage after transient ischemia in diabetic animals. The present study was designed to clarify whether the anticipated worse outcome after transient cerebral ischemia in diabetic animals was due to augmented leukocyte-mediated neural injury. Using rats with streptozotocin-induced diabetes of 4-wk duration, we investigated leukocyte-endothelial cell interactions during reperfusion after a transient 60-min period of retinal ischemia. Unexpectedly, postischemic diabetic retina showed no active leukocyte-endothelial cell interactions during reperfusion. The maximal numbers of rolling and accumulating leukocytes in diabetic retina were reduced by 73.6 and 41.2%, respectively, compared with those in nondiabetic rats. In addition, neither preischemic insulin treatment of diabetic rats nor preischemic glucose infusion of nondiabetic rats significantly influenced leukocyte-endothelial cell interactions during reperfusion. The present study demonstrated that high blood glucose concentration before induction of ischemia did not exacerbate leukocyte involvement in the postischemic retinal injury. Furthermore, diabetic retina showed suppressed leukocyte-endothelial cells interactions after transient ischemia, perhaps due to an adaptive mechanism that developed during the period of induced diabetes.