NADPH REDUCTASES AND POLYOL PATHWAY IN OCULAR COMPLICATIONS

喂食半乳糖的狗会出现视网膜毛细血管变化，这些变化 类似于人类糖尿病视网膜病变。这种动物模型不能发展成 只有早期的毛细血管改变，如微动脉瘤和各种大小 视网膜出血的同时也是晚期增生性疾病 新血管长入玻璃体的变化。这表明 就像人类的视网膜病变一样，视网膜毛细血管的阻塞 这是喂食半乳糖的狗发生视网膜变化的基础。至 了解毛细血管闭塞的机制，这启动了 这些视网膜病变，我们的研究一直集中在 视网膜毛细血管细胞与白细胞的相互作用。 饲喂30%半乳糖饲料的狗同时表现出淋巴细胞和 中性粒细胞功能障碍。凝集素诱导的成纤维细胞 从喂食半乳糖的狗中分离出的淋巴细胞显著减少。 比非半乳糖血症对照犬要高。尽管许多中性粒细胞 趋化性等功能在正常范围内，诱导 饲喂半乳糖的狗NADPH氧化酶降低。狗中性粒细胞 通过各种刺激物如肿瘤坏死因子-α、PMA和 环己亚胺。这三种刺激剂诱导的细胞凋亡 在喂食半乳糖的狗中显著抑制。尽管表面上 半乳糖喂养的中性粒细胞对细胞凋亡的抑制作用 狗与视网膜的互动显著增加 毛细血管内皮细胞。因为感染的发生率更高 发生在糖尿病患者身上，并对各种 糖尿病患者的炎症往往比 在非糖尿病患者中，激活的中性粒细胞的相互作用增加可能 启动或加速观察到的毛细血管闭塞 糖尿病视网膜病变。

Dogs fed galactose diet develop retinal capillary changes that are similar to human diabetic retinopathy. This animal model develops not only early capillary changes such as microaneurysms and various sizes of retinal hemorrhages but also the advanced stage of proliferative changes where new vessels grow into vitreous body. This indicates that, like human retinopathy, the occlusion of retinal capillaries underlie the development of retinal changes in galactose-fed dogs. To understand the mechanism of capillary occlusion, which initiates these retinal lesions, our research has been focussed on the interaction of retinal capillary cells and leukocytes. Dogs placed on 30% galactose diet displayed both lymphocyte and neutrophil dysfunction. Blastformation induced by lectins of lymphocytes isolated from galactose-fed dogs was significantly lower than that of non-galactosemic control dogs. Although many neutrophil functions such as chemotaxis were in the normal range, induction of NADPH oxidase was decreased in galactose-fed dogs. Dog neutrophils undergo apoptosis by various stimulants such as TNF-alpha, PMA and cycloheximide. Apoptosis induced by these three stimulants was significantly suppressed in galactose-fed dogs. Despite the apparent suppression of apoptosis, neutrophils isolated from galactose-fed dogs demonstrated a dramatically increased interaction with retinal capillary endothelial cells. Since a higher incidence of infection occurs in patients with diabetes and the reaction to various inflammations tends to be more severe in diabetics than non-diabetics, the increased interaction of activated neutrophils may either initiate or accelerate capillary occlusion observed in diabetic retinopathy.