3　讨论

　　近年来近视之药物治疗徘徊不前，仅有的有效药物阿托品［覃毒硷(muscarine)对抗药］也是在临床研究中发现能防止近视之进行。动物实验中发现了很多种视网膜制造的生长因子(bFGF、HGF、TGF-β)、激素［褪黑激素(melatonin)、5-羟色胺(serotonin)、vasoactive intestine polypeptide(VIP)］和神经递质［覃毒硷、多巴胺(dopamine)］均能促进或抑止近视之发生^［2～4］。按理说这些发现必将促进近视的药物治疗发展。但迄今为止，此类物质或其对抗药物均未能用于近视之药物治疗，原因何在值得探讨。

　　我们发现脉络膜黑素细胞具有褪黑激素与覃毒硷等近视信使之受体^［5，6］，因此提出假设：由于黑素细胞具有近视信使之受体，因此此类物质无法直接到达并作用于巩膜，对近视发挥作用^［1］。

　　实验研究发现，近视发生时，眼部bFGF含量下降而TGF-β₂含量上升。眼部注射bFGF能抑止近视之发生，而TGF-β₂能对抗bFGF，有防止近视作用^［2，7］。在鼠眼球生长基因研究中，发现制造HGF之基因可能与眼球生长密切相关，因此HGF也可能影响近视之发生^［8］。

　　生长因子在眼部之产生部位尚无定论，一般认为可能在视网膜产生^{［14～15］}。本项研究发现RPE与脉络膜成纤维细胞均能制造bFGF、HGF、与TGF-β₂，提示影响近视发生之生长因子也可能源自RPE与脉络膜。bFGF、HGF与TGF-β₂能影响RPE、黑素细胞与成纤维细胞之生长，表明这些细胞也必有此类生长因子的受体存在。

表2　近视信使的受体在色素上皮—脉络膜细胞中存在的情况

　　Tab.2　The presence of receptors of retina-originated messengers related to

　　myopia in the cells located in the RPE-choroid

　　*It has been demonstrated that melanin in the cultured RPE and melanocytes can reduce the amount of exogenous nitric oxide in the culture medium

图2　视网膜产生的信使阻止位于色素上皮一脉络膜的各类细胞，

　　使它们不能到达巩膜，从而阻滞或减轻近视发生的作用。

　　Fig.2　Retina-originated messengers bind to various cell types located in the

　　RPE-choroid,so that they cannot enter the sclera to express they effects.

　　Their effects are blocked or reduced.

图3　视网膜产生的信使激发色素上皮-脉络膜上的各类细胞释

　　放其他信使作用于巩膜而影响近视的发生。

　　Fig.3　Retina-oringinated messengers stimulate various cell types located in the

　　RPE-choroid to release other messengers to affect the sclera

　　and play a role in the occurrence of myopia.

　　进一步复习文献及回顾我们过去的研究，发现RPE、黑素细胞与成纤维细胞具有上述所有能影响近视的生长因子、激素及神经递质的受体(表2)^{［1，5，6，19～20］}。因此证明并扩大了我们假设的范围，即已知的由神经视网膜制造的与近视有关的生化物质，无一能顺利透过RPE与脉络膜而直接作用于巩膜。RPE与脉络膜内各种细胞之作用可能为：①这些细胞可与各种近视信使结合，阻断其作用(图2)。②各种近视信使与RPE等细胞结合后能刺激或抑止这些细胞制造与近视有关的生化物质，从而作用于巩膜而影响近视之发生(图3)。RPE与脉络膜对近视的确切作用还有待研究。如能了解经RPE和脉络膜级联系统(cascade)产生的最终近视信使，必能为近视的药物治疗提供重要信息。因此，对RPE—脉络膜与近视关系的深入研究，除有助于了解近视之发病机制外，并可为近视药物治疗带来新的希望。

　　基金项目：Supported by the New York Eye and Ear Infirmary Departments of Ophthalmology and Pathology Research Funds。

　　作者简介：胡诞宁，男，上海人，旅美学者，纽约医学院眼科教授、纽约眼耳鼻喉科医院组织培养研究中心主任。

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收稿日期：2000-08-09

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