Vitreous from patients with proliferative diabetic retinopathy contains an angiogenic substance which stimulates the proliferation of blood vessels on the chick chorioallantoic membrane, whereas vitreous from non-diabetics who do not have a proliferative retinopathy does not.
SUMMARY Minor and major deficiencies of enzymes affecting galactose metabolism may be associated with cataracts of early onset. Results are presented for 10 such families with minor enzymatic disorders. Expression of the major disorders probably involves galactitol accumulation and osmotic lens damage but this mechanism is not obviously associated with minor disorders. The observed incidence of minor incomplete enzymatic disorders of galactose metabolism in families with an incidence of cataracts of early onset may be at least partly incidental.Major restriction of the normal pathways of galactose metabolism is associated with a high risk of cataract, as in homozygous deficiency of galactokinase or galactose-1-phosphate uridyl transferase, disorders involving transferase deficiency arising through low-activity variant forms, and these defects in various combinations. Heterozygous and lesser deficiencies, particularly of galactokinase, occur in families with an incidence of presenile cataracts,'-3 and minor deficiencies have also been found in mothers of enzymatically normal children with congenital cataracts, suggesting indirect influences during pregnancy.4Disorders of galactose metabolism may therefore have a more pervasive influence on the risk of cataract than is suggested by the incidence of the rare major disorders, and expression may be controlled by early recognition and dietary change. For the major disorders there is strong although partly indirect evidence that cataract arises through increased availability of galactose, with galactitol accumulation and osmotically-induced damage within the lens,5 6 and the risk of cataract also broadly associates with the extent of galactose intolerance.7 If the partial disorders are in similar direct relationship to the risk of cataract it may be possible to identify factors contributing to the wide variation of effect seen, and to identify individuals particularly at risk.We have investigated the activity of galactose enzymes, and in some cases oral galactose tolerance, in families with an incidence of early onset and probably congenital bilateral cataracts. As with previous studies, abnormalities were
SUMMARY A low-molecular-weight angiogenic factor has been isolated from healthy adult cat retinas. The factor, which has been purified by diethylaminoethyl (DEAE) cellulose chromatography and affinity chromatography, stimulates neovascularisation of the chick chorioallantoic membrane and has a number of properties similar to those previously described for a tumour factor. The finding of an angiogenic factor in healthy retina and its relationship to previously described inhibitors of angiogenesis is discussed.Retinal neovasularisation can be a serious complication in a number of ocular disorders. 2 The observation that retinal capillary malperfusion often precedes neovascularisation'5 and furthermore that destruction of the areas of nonperfused retina results in regression of the newly formed vessels67 has suggested that a diffusable substance with vasoproliferative properties may be formed by the ischaemic retina. Direct evidence for a retina-derived angiogenic factor has recently been reported. Federmann et al.8 observed the growth of limbal vessels toward implants of retinal tissue in rabbit corneas, and other workers"'3 have demonstrated the presence of angiogenic activity in extracts of retinal tissue.In this report we describe the purification of a factor from feline retina which in a crude form has been shown to stimulate growth of the limbal vessels into the rabbit cornea.9 Preliminary studies indicate that the factor has a low molecular weight and resembles a factor isolated from rat Walker 256 tumours" 15 and from the synovial fluid of diseased joints. 16 Materials and methodsAdult cats aged 4-6 years from the Institute of Ophthalmology colony were used in these studies. They were administered an overdose of pentobarbital (Sagatal), and the eyes were enucleated when the animals were under deep anaesthesia. The retinas Correspondence to Dr J. B. Weiss.were removed immediately under sterile distillea water at 4°C. Batches of 8 retinas were pooled and stored at -40°C.The retinas (1 batch, 8 retinas) were thawed and homogenised for 1 minute at 4°C in a glass PotterElvehjem homogeniser. The homogenate was incubated at 4°C for 30 minutes and then spun at 600 g for 15 minutes at 4°C. The supernatant was collected and the pellet re-extracted as described above. Both supernatants were pooled and spun at 100000 g for 1 hour at 4°C, when the clear supernatant was decanted and purified by diethylaminoethyl (DEAE) cellulose column chromatography and by affinity chromatography using a modification of the method described for the purification of a tumour angiogenic factor. '4 DEAE CELLULOSE CHROMATOGRAPHY Solid ammonium bicarbonate was added to the 100000 g supernatant to give a final concentration of 50mM salt. This sample was applied to a column (8x 1 cm) of DEAE cellulose (Whatman) equilibrated with 50 mM NH4HCO3 (pH 7 9) at 4°C. Unbound material was eluted with the same buffer at a flow rate of 50 ml/h. The column effluent was monitored at 280 nm (Uvicord S, LKB, Sweden) and 14 ml fractions were collected. Bound m...
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