Nguyen-Legros J, Hicks D
Institut National de la Santé et de la Recherche Médicale (INSERM, U-450) Laboratoire de NeuroCytologie Oculaire, Paris, France.
Int Rev Cytol. 2000;196:245-313. doi: 10.1016/s0074-7696(00)96006-6.
The discovery of disc protein renewal in rod outer segments, in 1960s, was followed by the observation that old discs were ingested by the retinal pigment epithelium. This process occurs in both rods and cones and is crucial for their survival. Photoreceptors completely degenerate in the Royal College of Surgeons mutant rat, whose pigment epithelium cannot ingest old discs. The complete renewal process includes the following sequential steps involving both photoreceptor and pigment epithelium activity: new disc assembly and old disc shedding by photoreceptor cells; recognition and binding to pigment epithelium membranes; then ingestion, digestion, and segregation of residual bodies in pigment epithelium cytoplasm. Regulating factors are involved at each step. While disc assembly is mostly genetically controlled, disc shedding and the subsequent pigment epithelium phagocytosis appear regulated by environmental factors (light and temperature). Disc shedding is rhythmically controlled by an eye intrinsic circadian oscillator using endogenous dopamine and melatonin as light and dark signal, respectively. Of special interest is the regulation of phagocytosis by multiple receptors, including specific phagocytosis receptors and receptors for neuroactive substances released from the neuroretina. The candidates for phagocytosis receptors are presented, but it is acknowledged that they are not completely known. The main neuromodulators are adenosine, dopamine, glutamate, serotonin, and melatonin. Although the transduction mechanisms are not fully understood, attention was brought to cyclic AMP, phosphoinositides, and calcium. The chapter points to the multiplicity of regulating factors and the complexity of their intermingling modes of action. Promising areas for future research still exist in this field.
20世纪60年代，人们发现视杆外段存在盘膜蛋白更新现象，随后观察到旧的盘膜被视网膜色素上皮细胞吞噬。这一过程在视杆细胞和视锥细胞中均会发生，对它们的存活至关重要。在皇家外科学院突变大鼠中，光感受器会完全退化，因为其色素上皮细胞无法吞噬旧的盘膜。完整的更新过程包括以下一系列涉及光感受器和色素上皮细胞活动的步骤：光感受器细胞进行新盘膜组装和旧盘膜脱落；旧盘膜识别并结合到色素上皮细胞膜；然后色素上皮细胞质对残体进行吞噬、消化和分离。每个步骤都涉及调节因子。虽然盘膜组装主要受基因控制，但盘膜脱落以及随后的色素上皮细胞吞噬作用似乎受环境因素（光和温度）调节。盘膜脱落由眼睛内在的昼夜节律振荡器有节奏地控制，该振荡器分别以内源性多巴胺和褪黑素作为光信号和暗信号。特别值得关注的是多种受体对吞噬作用的调节，包括特定的吞噬受体和从神经视网膜释放的神经活性物质的受体。文中列出了吞噬受体的候选者，但也承认尚未完全明确它们。主要的神经调节因子有腺苷、多巴胺、谷氨酸、血清素和褪黑素。尽管转导机制尚未完全了解，但已关注到环磷酸腺苷、磷酸肌醇和钙。本章指出了调节因子的多样性及其相互作用模式的复杂性。该领域仍存在有前景的未来研究方向。
