Department of Ophthalmology, The Hebrew University-Hadassah Schools of Medicine and Dental Medicine, Jerusalem, Israel.
J Ocul Pharmacol Ther. 2009 Dec;25(6):475-82. doi: 10.1089/jop.2009.0020.
Recent evidence suggests that oxidative injury plays a significant role in the pathogenesis of retinal degenerative diseases. Para-aminobenzoic acid (PABA) is a cyclic amino acid, which may act to decrease lipid peroxidation and oxidative injury. Our aim was to evaluate the efficacy of PABA in attenuating oxidative injury and rate of retinal degeneration in the rd10 mouse.
PABA (50 mg/kg) was administered intraperitoneally six times per week in 28 rd10 mice from postnatal day 3. Twenty-four littermate control mice were similarly injected with saline. At 3, 4.5, and 6 weeks of age, electrophysiological (full field electroretinogram-ERG), quantitative histological, and immunohistochemical techniques were used to assess the course and extent of retinal degeneration. Degree of lipid peroxidation was determined by the measurement of thiobarbituric acid reactive species (TBARS) and retinal carbonyl content was quantified using the 2,4-dinitrophenylhydrazine method.
Dark adapted mixed rod-cone ERG responses at 3 weeks of age were higher in the PABA-treated group as compared to saline control (P < 0.05). By 4.5 weeks, this protective effect was largely abolished and by 6 weeks ERG was unrecordable in both groups. However, at both 3 and 4.5 weeks of age, light-adapted cone ERG amplitudes were better preserved in PABA-treated animals. At 4.5 weeks, thickness of the outer nuclear layer was 28.6% higher in the peripheral retina of PABA-treated mice as compared to controls (P < 0.05). Quantitative immunohistochemistry revealed 2.4-fold higher red/green cone opsin content in the retinas of PABA-treated mice (P < 0.005). At both 3 and 4.5 weeks, levels of TBARS and protein carbonyls were 49%-69% lower in PABA-treated retinas (P < 0.05-0.0005), suggesting less oxidative injury.
PABA treatment may protect retinal function and attenuate the course of retinal degeneration in rd10 mice. Biochemical parameters indicate a lower degree of oxidative injury in PABA-treated retinas. PABA may potentially serve as an addition to antioxidative treatment for retinal and macular degenerations.
最近的证据表明，氧化损伤在视网膜退行性疾病的发病机制中起着重要作用。对氨基苯甲酸（PABA）是一种环状氨基酸，可能具有降低脂质过氧化和氧化损伤的作用。我们的目的是评估 PABA 减轻 rd10 小鼠氧化损伤和视网膜变性速度的效果。
从出生后 3 天开始，每周 6 次向 28 只 rd10 小鼠腹膜内注射 PABA（50mg/kg）。24 只同窝对照小鼠同样注射生理盐水。在 3、4.5 和 6 周龄时，使用全视野视网膜电图（ERG）、定量组织学和免疫组织化学技术评估视网膜变性的过程和程度。通过测量硫代巴比妥酸反应性物质（TBARS）来确定脂质过氧化程度，并用 2,4-二硝基苯肼法定量测定视网膜羰基含量。
在 3 周龄时，黑暗适应的混合棒状-锥状 ERG 反应在 PABA 治疗组中高于盐水对照组（P<0.05）。到 4.5 周时，这种保护作用几乎被消除，而在两组中，6 周龄时的 ERG 均无法记录。然而，在 3 周和 4.5 周龄时，PABA 治疗动物的光适应锥状 ERG 幅度更好地得到了保存。在 4.5 周龄时，PABA 治疗小鼠的外核层厚度在周边视网膜比对照组高 28.6%（P<0.05）。定量免疫组织化学显示，PABA 治疗小鼠的红/绿视锥蛋白含量高 2.4 倍（P<0.005）。在 3 周和 4.5 周龄时，PABA 治疗视网膜中的 TBARS 和蛋白质羰基水平分别降低了 49%-69%（P<0.05-0.0005），表明氧化损伤程度较低。
PABA 治疗可能保护视网膜功能并减轻 rd10 小鼠的视网膜变性过程。生化参数表明，PABA 治疗的视网膜中氧化损伤程度较低。PABA 可能作为视网膜和黄斑变性的抗氧化治疗的补充。
