Zhao Wei, Dai Le, Xi Xiao-Ting, Chen Qian-Bo, An Mei-Xia, Li Yan
Department of Ophthalmology, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China.
Department of Ophthalmology, the First Affiliated Hospital of Dali University, Dali 671000, Yunnan Province, China.
Int J Ophthalmol. 2020 Apr 18;13(4):525-534. doi: 10.18240/ijo.2020.04.01. eCollection 2020.
To investigate the relationships between the changes of heat shock protein 27 antibody (anti-HSP27) in serum/cerebrospinal fluid (CSF), intraocular pressure (IOP), retinal ganglion cell (RGC) apoptosis in a rat glaucoma model and disclose the underlying pathogenesis of glaucoma.
A total of 115 Wistar rats were randomly divided into 4 groups. Group 1 was the ocular hypertension group by condensing 3 episcleral & limbal veins or episcleral area of right eye (HP group, =25) and sham operation group with conjunctiva incision without coagulation (=25). Group 2: HSP27 or dose-matched PBS was injected into the vitreous (V-HSP27 group, =15; V-PBS group, =15). Group 3: HSP27 and complete Freund's adjuvant or dose-matched PBS was injected subcutaneously into the hind limb accompanied intraperitoneal injection of pertussis toxin [sensitized group (I-HSP27 group), =15; I-PBS group, =15)]. Group 4 was normal group without any treatment (=5). IOPs of the rats were measured before, day 3, weeks 1, 2, 4, 6, and 8 after treatment. Paraffin-embedded sections were prepared for HE staining and RGCs apoptosis were detected by TUNEL. Anti-HSP27 level in serum and CSF were examined by ELISA.
IOPs were elevated significantly in HP and V-HSP27, V-PBS groups (<0.01) and positively related to anti-HSP27 levels in serum and CSFs. Anti-HSP27 levels in serum and CSF were elevated significantly in I-HSP27 group compared to other groups (<0.05). However, the IOPs did not show any relationship with the high-level anti-HSP27 in serum and CSFs. RGC apoptosis were all elevated significantly in the HP, V-HSP27, V-PBS and I-HSP27 groups and also positively relative with anti-HSP27 level in serum and CSFs except that high-level of anti-HSP27 in the serum of I-HSP group.
The increases of anti-HSP27 levels in serum and CSFs both promote IOP escalation and the increase of RGC apoptosis in retina when anti-HSP27 is at low level. The case of high-level anti-HSP27 is opposite and shows protective function in preventing IOP increase and RGC apoptosis.
研究大鼠青光眼模型血清/脑脊液（CSF）中热休克蛋白27抗体（抗HSP27）变化、眼压（IOP）、视网膜神经节细胞（RGC）凋亡之间的关系，揭示青光眼的潜在发病机制。
115只Wistar大鼠随机分为4组。第1组为右眼3条巩膜及角膜缘静脉或巩膜区冷凝造高眼压组（HP组，n = 25）和仅结膜切开不凝血的假手术组（n = 25）。第2组：将HSP27或剂量匹配的PBS注入玻璃体（玻璃体注射HSP27组，n = 15；玻璃体注射PBS组，n = 15）。第3组：将HSP27与完全弗氏佐剂或剂量匹配的PBS皮下注射到后肢，并腹腔注射百日咳毒素[致敏组（皮下注射HSP27组），n = 15；皮下注射PBS组，n = 15]。第4组为未作任何处理的正常组（n = 5）。在治疗前、治疗后第3天、第1、2、4、6和8周测量大鼠眼压。制备石蜡包埋切片进行HE染色，采用TUNEL法检测RGC凋亡。采用ELISA法检测血清和CSF中的抗HSP27水平。
HP组、玻璃体注射HSP27组和玻璃体注射PBS组眼压显著升高（P<0.01），且与血清和CSF中的抗HSP27水平呈正相关。皮下注射HSP27组血清和CSF中的抗HSP27水平较其他组显著升高（P<0.05）。然而，眼压与血清和CSF中高水平的抗HSP27无相关性。HP组、玻璃体注射HSP27组、玻璃体注射PBS组和皮下注射HSP27组RGC凋亡均显著增加，除皮下注射HSP27组血清中抗HSP27水平高外，也与血清和CSF中的抗HSP27水平呈正相关。
血清和CSF中抗HSP27水平升高在抗HSP27处于低水平时均促进眼压升高和视网膜RGC凋亡增加。抗HSP27高水平时情况相反，对防止眼压升高和RGC凋亡具有保护作用。
