胆固醇是细胞膜的重要组成部分,对于保持其结构和功能的完整性至关重要。它对神经组织尤其重要,包括视网膜,它依赖于大量的质膜来传递神经信号。虽然胆固醇是迄今为止含量最丰富的甾醇,视网膜还含有胆固醇前体和代谢物,尤其是氧固醇,是生物活性分子。胆固醇缺乏或过量是有害的,并且已知一些氧固醇对神经元存活的影响。因此必须维持胆固醇稳态。视网膜胶质细胞,尤其是穆勒细胞,脊椎动物视网膜的主要神经胶质细胞,提供机械,营养,以及对邻近神经元的代谢支持。一些证据表明Müller细胞是视网膜胆固醇稳态的主要参与者,因为它是已知的其他神经胶质细胞在大脑中。这个过程是基于与神经元的密切合作,甾醇可以是参与神经胶质-神经元相互作用的信号分子。虽然现在已经认识到胆固醇在年龄相关性黄斑变性中的一些含义,根据流行病学和实验室数据,关于其在青光眼中作用的证据仍然很少。胆固醇血症和青光眼之间的关联是有争议的,但是实验数据表明,甾醇可以参与病理过程。已经证明Müller神经胶质细胞通过矛盾的反应性视网膜神经胶质增生过程与青光眼的发展有关。早期步骤有助于维持视网膜稳态并有利于神经节细胞的存活,这是青光眼期间的目标。如果神经胶质增生持续存在,神经保护功能失调,神经胶质细胞的Müller细胞的细胞毒性作用和神经胶质-神经元相互作用的破坏导致神经节细胞死亡加速。甾醇可能在胶质细胞对青光眼损伤的反应中起作用。这是一个未被研究但有吸引力的话题,可以更好地了解青光眼并构思新颖的预防或治疗策略。本综述描述了关于i)视网膜胶质细胞中甾醇代谢的最新知识,ii)胆固醇在青光眼中的潜在作用,和iii)胆固醇和氧固醇之间的可能关系,胶质细胞和青光眼。重点放在神经胶质-神经元的相互作用上。
Cholesterol is an essential component of cellular membranes, crucial for maintaining their structural and functional integrity. It is especially important for nervous tissues, including the retina, which rely on high amounts of plasma membranes for the transmission of the nervous signal. While cholesterol is by far the most abundant
sterol, the retina also contains cholesterol precursors and metabolites, especially oxysterols, which are bioactive molecules. Cholesterol lack or excess is deleterious and some oxysterols are known for their effect on neuron survival. Cholesterol homeostasis must therefore be maintained. Retinal glial cells, especially Müller cells, the principal glial cells of the vertebrate retina, provide mechanical, nutritional, and metabolic support for the neighboring neurons. Several pieces of evidence indicate that Müller cells are major actors of cholesterol homeostasis in the retina, as it is known for other glial cells in the brain. This process is based on a close cooperation with neurons, and sterols can be signaling molecules participating in glia-neuron interactions. While some implication of cholesterol in age-related macular degeneration is now recognized, based on epidemiological and laboratory data, evidence for its role in glaucoma is still scarce. The association between cholesterolemia and glaucoma is controversial, but experimental data suggest that sterols could take part in the pathological processes. It has been demonstrated that Müller glial cells are implicated in the development of glaucoma through an ambivalent reactive retinal gliosis process. The early steps contribute to maintaining retinal homeostasis and favor the survival of ganglion cells, which are targeted during glaucoma. If gliosis persists, dysregulation of the neuroprotective functions, cytotoxic effects of gliotic Müller cells and disruption of glia-neuron interactions lead to an acceleration of ganglion cell death. Sterols could play a role in the glial cell response to glaucomatous injury. This represents an understudied but attractive topic to better understand glaucoma and conceive novel preventive or curative strategies. The present review describes the current knowledge on i)
sterol metabolism in retinal glial cells, ii) the potential role of cholesterol in glaucoma, and iii) the possible relationships between cholesterol and oxysterols, glial cells and glaucoma. Focus is put on glia-neuron interactions.