Department of Ophthalmology and Pharmacology, Hôpital Sainte-Justine Research Center, Montreal, Canada.
Invest Ophthalmol Vis Sci. 2011 Aug 5;52(9):6238-48. doi: 10.1167/iovs.10-6742.
Retinopathy of prematurity (ROP) is a major cause of visual handicap in the pediatric population. To date, this disorder is thought to stem from deficient retinal vascularization. Intriguingly, functional electrophysiological studies in patients with mild or moderate ROP and in the oxygen-induced retinopathy (OIR) model in rats reveal central photoreceptor disruption that overlies modest retinal vessel loss; a paucity of retinal vasculature occurs predominantly at the periphery. Given that choroidal circulation is the major source of oxygen and nutrients to the photoreceptors, the authors set out to investigate whether the choroidal vasculature system may be affected in OIR.
Rat models of OIR treating newborn animals with 80% or 50/10% alternated oxygen level for the first two postnatal weeks were used to mimic ROP in humans. Immunohistology staining and vascular corrosion casts were used to investigate the vessel layout of the eye. To investigate the effect of 15-deoxy-Δ12,14-PGJ(2) (15d-PGJ(2); a nonenzymatic product of prostaglandin D(2)) on endothelial cells, in vitro cell culture and ex vivo choroid explants were employed and intravitreal injections were performed in animals.
The authors herein demonstrate that deficient vascularity occurs not only in the retinal plexus but also in the choroid. This sustained, marked choroidal degeneration is specifically confined to central regions of the retina that present persistent photoreceptor loss and corresponding functional deficits. Moreover, the authors show that 15d-PGJ(2) is a prominent contributor to this choroidal decay.
The authors demonstrate for the first time pronounced, sustained choroidal vascular involution during the development of ROP. Findings also suggest that effective therapeutic strategies to counter ROP should consider choroidal preservation.
早产儿视网膜病变（ROP）是儿科人群视力障碍的主要原因。迄今为止，这种疾病被认为源于视网膜血管生成不足。有趣的是，对轻度或中度 ROP 患者以及在大鼠氧诱导视网膜病变（OIR）模型中的功能电生理学研究表明，中央光感受器破坏超过了适度的视网膜血管损失；视网膜血管系统主要发生在外周。由于脉络膜循环是光感受器的主要氧气和营养来源，作者着手研究 OIR 中脉络膜血管系统是否可能受到影响。
作者使用了 OIR 的大鼠模型，即用 80%或 50/10%的交替氧气水平处理新生动物，以模拟人类的 ROP。免疫组织化学染色和血管腐蚀铸型用于研究眼睛的血管布局。为了研究 15-脱氧-Δ12,14-PGJ2（15d-PGJ2；前列腺素 D2 的非酶产物）对内皮细胞的影响，采用体外细胞培养和离体脉络膜外植体，并在动物中进行了眼内注射。
作者在此证明，不仅在视网膜丛中而且在脉络膜中都存在血管不足。这种持续的、明显的脉络膜退化仅局限于视网膜的中央区域，这些区域存在持续的光感受器丧失和相应的功能缺陷。此外，作者表明 15d-PGJ2 是导致这种脉络膜衰减的主要原因。
作者首次证明了在 ROP 发展过程中明显的、持续的脉络膜血管萎缩。研究结果还表明，有效的治疗 ROP 的策略应考虑到脉络膜的保存。
