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3.2 Drusen的形成[19]
另一种AMD的病理成分是drusen，是沉积在RPE细胞和Bruch膜内胶原带之间的区域无定形沉积物。Drusen是AMD的特征。临床上，相对大小和形状不同分为硬性和软性的。虽然小的硬疣（＜63μm）在临床上老年人群中95%可以发现，数个大的硬疣（≥125μm），尤其是黄斑区的软疣（≥12~250μm），尤其当有色素紊乱或色素脱失时，被认为是发生进展期AMD主要的危险因素。事实上，包括小的硬疣，drusen上面的光感受器发生了退行性变化。Drusen的形成是一个数年缓慢发生的复杂的多因素过程，drusen的形成对RPE和光感受器的影响包括物质的替代和通过免疫系统和局部炎症活化的间接影响。Drusen蛋白质和免疫组化的分析，分离出几种蛋白成分：包括数种免疫相关成分或分子，如树突状细胞突、免疫球蛋白、II型抗原、补体级联反应得成分，如激活剂、抑制剂、特异性活化补体片段；和终端途径成分，包括膜攻击复合物（MAC；C5b9），后者对外来病原体和局部宿主细胞和组织（如RPE，光感受器，和其他眼结构）都是致死性的[20]。补体系统是固有免疫系统的主要成分。局部炎症和补体级联反应的活化同时伴有MAC的产生，可以促进drusen的形成，RPE和光感受器变性，和Bruch膜破坏（与晚期的新生血管性AMD相关）[21]。近期基因研究证明在定位于1号染色体（1q31）CFH基因的氨基酸402（Y402H）发生酪氨酸和组氨酸的突变会增加AMD的发病危险。因为CFH可以阻断无法控制的补体激活和炎症过程，这种突变会促进炎症和加重其结果[22,23]。
4脉络膜新生血管
成人的视网膜是一个高代谢和高耗氧的神经组织。视网膜和脉络膜血管同时供应视网膜。视网膜的血管供应到外丛状层以内，供应视网膜内2/3层的氧气和营养，外1/3层无血管，但是它通过脉络膜血管接受营养和氧气。在正常情况下，由于促新生血管生长因子和抗新生血管生长因子之间保持平衡，这些细胞相对静止，血管内皮细胞对新生血管的刺激是有抵抗的，因此视网膜血管很少发生内皮细胞增生。低氧或缺血会导致VEGF、整合素和蛋白酶上调，这些因子的平衡被打破[24，25]。VEGF的信号强于PEDF时，会导致促新生血管生长因子增强，刺激新生血管生长，包括脉络膜新生血管（choroidal neovasculartization,CNV)[26]。实际上，中性粒细胞、巨噬细胞、肥大细胞、活化的小胶质细胞都可以产生和释放VEGF等因子，现在认为是局部炎症和免疫反应引起促新生血管因子增加导致了CNV的发生[27,28]。
总之，近年来很多研究应用免疫组化和分子生物学方法研究AMD的发病，结果表明炎性过程的局部活化，导致活化的补体成分、急性期反应物、免疫调节物和其它炎性因子的聚集参与了AMD发生的过程。现在的药物多针对VEGF以对抗新生血管[29]，未来会出现更多对抗细胞内和细胞外这些细胞毒性沉积物以阻断炎症过程的药物，从而从发病早期阻止疾病进一步发展。
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