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• We have used the electron microscopic immunogold technique to localize precisely various extracellular matrix components in human retinal vessels and Bruch's membrane. Collagen types IV and V, laminin, and heparan sulfate proteoglycan core protein were localized in basement membranes of retinal capillaries. In addition to the capillary basement membrane components, collagen types I and III and fibronectin were found in the basement membranes of retinal arterioles and venules. The basement membranes of choriocapillaries and retinal pigment epithelial cells in Bruch's membrane also showed a similar distribution of the retinal capillary basement membrane components. Both the inner and outer collagenous layers of Bruch's membrane contained collagen types I and III along with fibronectin, whereas collagen type VI was mostly limited to the central elastic lamina. The precise localization and distribution of various extracellular matrix components in human retinal vessels and Bruch's membrane may be important for understanding their normal function as well as their alteration in disease.

Twenty-four patients with proliferative or preproliferative diabetic retinopathy underwent extensive argon laser photocoagulation in one eye. Detailed central and peripheral visual-field examinations and electroretinography were performed before treatment, and at intervals after treatment.Visual field changes were as follows: (1) eight patients had only mild to moderate constriction of all isopters, (2) 11 had discrete scotomata in addition, (3) two had prominent nerve-fiber-bundle defects, (4) three had severe constriction of all isopters, save (in two) that to the largest peripheral test object. Electroretinographic b-wave amplitudes were reduced an average of 40% to white test flashes. Blue test flashes showed an even larger reduction of the rod response. This suggests the receptors in approximately 40% of the retinal area are destroyed by such extensive photocoagulation, covering predominantly that part of the retina that has the highest concentration of rods.

A 30-year-old Negro man presented with a subhyaloid and vitreous hemorrhage in the left eye. He had chronic myelogenous leukemia of four years' duration but had been untreated for the past year. The peripheral leukocyte count was 250,000/cu mm. Neovascular tufts arose from retinal arteriovenous shunts just anterior to the equator in the superior and temporal quadrants of both eyes. These extended into the vitreous, accompanied by fibrous proliferation. They resembled the proliferative fibrovascular lesions ("sea fans") seen in hemoglobin sickle cell-hemoglobin C retinopathy. This patient's hemoglobin was AA, however. He had no evidence of occlusive vascular disease, and the protein electrophoretic pattern and results of a glucose tolerance test were normal. Retinal neovascularization has not previously been reported as a consequence of leukemia.

In 1959, the British biochemist Ruth van Heyningen1 reported that the cataractous lenses of diabetic rats contain high concentrations of the sugar alcohol sorbitol, which is produced by reduction of the aldehyde group of glucose. Later work by Kinoshita2,3 demonstrated that the sorbitol is produced by the action of an enzyme, aldose reductase. Cataractogenesis by sugar alcohols was demonstrated more strikingly in nondiabetic animals fed galactose whose sugar alcohol, galactitol, unlike sorbitol, cannot be further oxidized to a keto sugar by sorbitol dehydrogenase. Hence, galactitol builds to high levels intracellularly faster than sorbitol, producing the same effects, but more rapidly.See also pp 1234 and 1301.Cataracts were the first complication of diabetes to be attributed to the "sorbitol pathway." As more investigators began to explore this pathway, the complexity of the chemical reactions affected by sugar alcohols was found to be greater than anticipated, as was the

Two research in the cellular mechanisms of diabetic retinopathy have been of major recent interest—the pathogenesis of the earliest functional and anatomic lesions of the disease and the pathogenesis of the retinal neovascularization that occurs in its late stages. Of these two research problems, the first is probably the most perplexing. What are the earliest structural and functional abnormalities in the retinas of diabetic subjects? What is their cause? How do they lead to further abnormality and, ultimately, to the clinical picture of advanced diabetic retinopathy with loss of vision, with which we are all familiar? In the early 1960s, Cogan, Kuwabara, and their colleagues,1 in the pages of the Archives, described the results of their trypsin digest studies of the retinal vessels of human diabetic subjects. They described the earliest anatomic lesions that have been detected thus far in diabetic retinopathy, namely, loss of the intramural pericytes (or

AN ACCURATE animal model of a human disease can help us to understand the pathogenesis of the disease, to study its cellular and molecular mechanisms of progression, and to test new therapeutic approaches before they are ready for evaluation in human subjects. The model of diabetic retinopathy in the long-term galactosemic dog, introduced by Engerman and Kern1 in 1984, is one of the best animal models now available in ophthalmic research. After 3 to 5 years on a diet containing 30% galactose, these animals accurately reproduce the lesions of early diabetic retinopathy in humans, and they do so following chronic elevation of an aldohexose that is structurally similar to glucose but does not enter into many of the biochemical pathways by which glucose is metabolized. In this issue of the Archives, Engerman and Kern2 and Kador et al3 report important new findings using this model that appear

IN REPLY We commend Dr Bloom for his thorough search of the literature dealing with the association of subretinal neovascular membranes and colobomas. Unfortunately, the entities described in his references 3 through 6 are colobomas of the retina and choroid, which occur because of defects in the closure of the fetal fissure.1,2 Both in their ophthalmoscopic appearance and in their developmental origin, these are quite different from the coloboma of the optic nerve reported by us and the related cavitary developmental lesions of the optic nerve (optic nerve "pits"; "morning glory syndrome") described in the references that we cited. By contrast with the colobomas of the retina and choroid that are described in all but one of the references cited by Dr Bloom, these defects are thought to be produced by abnormalities in the formation of the optic papilla.1,2 Perusal of the photographs in his references 3 through