Steck Janina, Blueml Carolin, Kampmann Susanne, Greene Brandon, Maier Rolf F, Arnhold Stefan, Gerstner Bettina, Stieger Knut, Lorenz Birgit
Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany.
Department of Pediatrics, Philipps-University Marburg, Marburg, Germany.
Invest Ophthalmol Vis Sci. 2015 Feb 19;56(3):1830-41. doi: 10.1167/iovs.14-15262.
To characterize concurrent retinal vessel pathologies reminiscent to retinopathy of prematurity (ROP) in a rat model of periventricular leukomalacia (PVL), in order to identify uniform damage pathways in both organs, the eye and the brain.
Ischemia was induced in Long Evans rat pups on postnatal day 6 (P6) with unilateral (left side) carotid ligation (UCL) followed by exposure to different oxygen concentrations. Four different groups were studied: group A, hypoxia/ischemia (UCL + 6% O2, 1 hour); group B, hyperoxia (80% O2, 24 hours); group C, hypoxia/ischemia + hyperoxia (UCL + 6% O2, 1 hour + 80% O2, 24 hours); and group D, normoxia. In groups A and C, both retinae were examined separately (left retina, group A [A-L], right retina, group A [A-R]; left retina, group C [C-L], right retina, group C [C-R]). Morphologic analysis of vessel development based on flatmounts and cryosections was performed at P11 and P21. Quantitative (q)PCR was performed at P7, P11, and P21 (VEGF-A164, HIF-1α, EpoR, TNFα, iNOS, BMP-9, and IGF-1).
On flatmounts, distinct retardation in deeper vascular plexus development was observed, most prominent in A-L and C-L. Retinae of groups A-L and C-L displayed reduced capillary-free zones and an increased number of branching points at P11. Quantitative PCR analysis showed significantly different expression profiles of IGF-1 in A-L and B compared with D over the time course of the experiment.
This is the first report on concurring damage to the retina that was evaluated in a rat model of white matter injury in the developing brain. The relatively mild damage to the retinal vessel system may represent the basis for a model of moderate forms of ROP and to study vascular remodeling.
在脑室周围白质软化（PVL）大鼠模型中，对并发的视网膜血管病变进行特征描述，这些病变类似于早产儿视网膜病变（ROP），以便确定眼睛和大脑这两个器官中统一的损伤途径。
在出生后第6天（P6）的Long Evans大鼠幼崽中诱导缺血，采用单侧（左侧）颈动脉结扎（UCL），随后暴露于不同的氧浓度下。研究了四个不同的组：A组，缺氧/缺血（UCL + 6% O₂，1小时）；B组，高氧（80% O₂，24小时）；C组，缺氧/缺血 + 高氧（UCL + 6% O₂，1小时 + 80% O₂，24小时）；D组，常氧。在A组和C组中，分别检查两个视网膜（A组左视网膜[A-L]，A组右视网膜[A-R]；C组左视网膜[C-L]，C组右视网膜[C-R]）。在P11和P21时，基于平铺标本和冰冻切片对血管发育进行形态学分析。在P7、P11和P21时进行定量（q）PCR（VEGF-A164、HIF-1α、EpoR、TNFα、iNOS、BMP-9和IGF-1）。
在平铺标本上，观察到深层血管丛发育明显迟缓，在A-L和C-L中最为突出。A-L组和C-L组的视网膜在P11时显示无毛细血管区减少，分支点数量增加。定量PCR分析显示，在实验过程中，与D组相比，A-L组和B组中IGF-1的表达谱有显著差异。
这是关于在发育中的大脑白质损伤大鼠模型中评估视网膜并发损伤的首次报告。视网膜血管系统相对较轻的损伤可能是中度ROP模型及研究血管重塑的基础。
