McLeod D Scott, Grebe Rhonda, Bhutto Imran, Merges Carol, Baba Takayuki, Lutty Gerard A
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland 21287-9115, USA.
Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4982-91. doi: 10.1167/iovs.09-3639. Epub 2009 Apr 8.
The purpose of this study was to examine the relationships between choriocapillaris (CC) and retinal pigment epithelial changes in age-related macular degeneration (AMD). Morphologic changes in the retinal pigment epithelium (RPE)/choriocapillaris complex were quantified in dry and wet forms of AMD, and the results were compared with those in aged control eyes without maculopathy.
Postmortem choroids from three aged control subjects, five subjects with geographic atrophy (GA), and three subjects with wet AMD were analyzed using a semiquantitative computer-assisted morphometric technique developed to measure the percentages of retinal pigment epithelial and CC areas in choroidal wholemounts incubated for alkaline phosphatase activity. The tissues were subsequently embedded in methacrylate and were sectioned so that structural changes could be examined.
There was a linear relationship between the loss of RPE and CC in GA. A 50% reduction in vascular area was found in regions of complete retinal pigment epithelial atrophy. Extreme constriction of remaining viable capillaries was found in areas devoid of RPE. Adjacent to active choroidal neovascularization (CNV) in wet AMD, CC dropout was evident in the absence of retinal pigment epithelial atrophy, resulting in a 50% decrease in vascular area. Lumenal diameters of the remaining capillaries in wet AMD eyes were similar to those in control eyes.
The primary insult in GA appears to be at the level of the RPE, and there is an intimate relationship between retinal pigment epithelial atrophy and secondary CC degeneration. CC degeneration occurs in the presence of viable RPE in wet AMD. The RPE in regions of vascular dropout are presumably hypoxic, which may result in an increase in VEGF production by the RPE and stimulation of CNV.
本研究旨在探讨年龄相关性黄斑变性(AMD)中脉络膜毛细血管(CC)与视网膜色素上皮变化之间的关系。对干性和湿性AMD中视网膜色素上皮(RPE)/脉络膜毛细血管复合体的形态学变化进行定量分析,并将结果与无黄斑病变的老年对照眼进行比较。
使用一种半定量计算机辅助形态测量技术,对3名老年对照受试者、5名患有地图样萎缩(GA)的受试者和3名患有湿性AMD的受试者的死后脉络膜进行分析,该技术用于测量经碱性磷酸酶活性孵育的脉络膜整体标本中视网膜色素上皮和CC区域的百分比。随后将组织包埋在甲基丙烯酸酯中并切片,以便检查结构变化。
GA中RPE和CC的丧失之间存在线性关系。在完全视网膜色素上皮萎缩区域发现血管面积减少50%。在无RPE的区域发现剩余存活毛细血管极度收缩。在湿性AMD中,邻近活跃的脉络膜新生血管(CNV)处,在无视网膜色素上皮萎缩的情况下CC缺失明显,导致血管面积减少50%。湿性AMD眼中剩余毛细血管的管腔直径与对照眼中相似。
GA中的主要损伤似乎发生在RPE水平,视网膜色素上皮萎缩与继发性CC变性之间存在密切关系。湿性AMD中在存活的RPE存在时发生CC变性。血管缺失区域的RPE可能缺氧,这可能导致RPE产生的VEGF增加并刺激CNV。