Ambati Jayakrishna, Ambati Balamurali K, Yoo Sonia H, Ianchulev Sean, Adamis Anthony P
Ocular Angiogenesis Laboratory, Department of Ophthalmology, University of Kentucky, Lexington, USA.
Surv Ophthalmol. 2003 May-Jun;48(3):257-93. doi: 10.1016/s0039-6257(03)00030-4.
Age-related macular degeneration is the principal cause of registered legal blindness among those aged over 65 in the United States, western Europe, Australia, and Japan. Despite intensive research, the precise etiology of molecular events that underlie age-related macular degeneration is poorly understood. However, investigations on parallel fronts are addressing this prevalent public health problem. Sophisticated biochemical and biophysical techniques have refined our understanding of the pathobiology of drusen, geographic atrophy, and retinal pigment epithelial detachments. Epidemiological identification of risk factors has facilitated an intelligent search for underlying mechanisms and fueled clinical investigation of behavior modification. Gene searches have not only brought us to the cusp of identifying the culpable gene loci in age-related macular degeneration, but also localized genes responsible for other macular dystrophies. Recent and ongoing investigations, often cued by tumor biology, have revealed an important role for various growth factors, particularly in the neovascular form of the condition. Transgenic and knockout studies have provided important mechanistic insights into the development of choroidal neovascularization, the principal cause of vision loss in age-related macular degeneration. This in turn has culminated in preclinical and clinical trials of directed molecular interventions.
年龄相关性黄斑变性是美国、西欧、澳大利亚和日本65岁以上人群法定失明登记的主要原因。尽管进行了深入研究，但对年龄相关性黄斑变性潜在分子事件的确切病因仍知之甚少。然而，多方面的研究正在解决这一普遍的公共卫生问题。先进的生化和生物物理技术加深了我们对玻璃膜疣、地图样萎缩和视网膜色素上皮脱离病理生物学的理解。危险因素的流行病学识别有助于明智地寻找潜在机制，并推动行为改变的临床研究。基因搜索不仅使我们即将确定年龄相关性黄斑变性中的致病基因位点，还定位了导致其他黄斑营养不良的基因。最近和正在进行的研究，通常受肿瘤生物学的启发，揭示了各种生长因子的重要作用，特别是在该疾病的新生血管形式中。转基因和基因敲除研究为脉络膜新生血管形成的发展提供了重要的机制见解，脉络膜新生血管形成是年龄相关性黄斑变性视力丧失的主要原因。这反过来又促成了定向分子干预的临床前和临床试验。
