近视眼局部生长调控研究进展

近视研究显示：在近视发病中存在着眼局部生长调控。本文对眼局部生长调控信号的来源、作用和靶组织,以及视网膜色素上皮层在信号传递过程中的作用进行了综述。     

Postnatal changes in lysosomal enzymes of rabbit ocular tissues

Postnatal changes in acid phosphatase, β-glucuronidase, arylsulfatase and cathepsin D in ocular tissues and liver were studied biochemically. Lysosomal enzymes, except for cathepsin D, showed postnatal age-dependent variations in activity. It is suggested that the changes in lysosomal enzyme activities in ocular tissues are related to eye development.     

Melatonin receptors in chick ocular tissues: implications for a role of melatonin in ocular growth regulation

PURPOSE: The influences of diurnal rhythms involving a variety of ocular parameters are implicated in the development of myopia. The purpose of this study was to determine the expression of the melatonin receptor subtype proteins in chick ocular tissues and to examine the role of the circadian signaling molecule melatonin in normal ocular growth and the exaggerated ocular growth associated with the development of myopia. METHODS: Expression of the Mel(1a), Mel(1b), and Mel(1c) melatonin receptor proteins in ocular tissues was examined by Western blot analyses, slot blot analyses, and immunocytochemistry. For examining the effect of melatonin on ocular growth, chicks were maintained on a 12-hour light-dark cycle and were monocularly form-vision deprived in one eye with a translucent occluder for 5 days. During the 5-day treatment period, chicks were injected systemically during the early dark period with melatonin (0.6 mg) or 2% ethanol vehicle control. Ocular dimensions of normal and deprived eyes were examined by high frequency A-scan ultrasound. RESULTS: Immunocytochemical analysis of chick ocular tissues revealed the cellular distribution of the Mel(1a) receptor subtype in the cornea, choroid, sclera, and retina. Western blot and slot blot analyses demonstrated that all three receptors were present in these tissues and they demonstrated distinct diurnal rhythms of protein expression in the retina-RPE-choroid, with peak levels of Mel(1a) and Mel(1b) occurring during the night and peak levels of Mel(1c) during the day. Systemic administration of melatonin resulted in significant changes in anterior chamber depth, vitreous chamber depth, and choroidal thickness of form-deprived and/or control eyes. CONCLUSIONS: Results of this study show that all three melatonin receptor subtypes are expressed in retinal and extraretinal ocular tissues of the chick eye. The finding that administration of melatonin alters the growth of several ocular tissues in both control and form-deprived eyes suggests that melatonin, acting through specific melatonin receptors in ocular tissues, plays a role in ocular growth and development. This conclusion suggests that the action of melatonin, combined with expression of melatonin receptors, is involved in the regulation of the diurnal rhythm of ocular growth.     

信号通路与近视眼局部生长调控研究进展

现有较多研究表明,近视发展中存在局部生长调控,许多信号分子参与了这一过程.本文对信号分子在近视眼局部调控生长中的信号通路及其调节作用进行了综述.     

The EEC syndrome and its ocular manifestations.

The EEC syndrome (ectrodactyly or lobster-claw deformity, ectodermal dysplasia, and cleft lip and palate) is a rare disorder with autosomal dominant inheritance, variable expression, and in some families lack of penetrance. We present the findings in five cases with emphasis on the ocular findings. Lacrimal surgery was performed on three patients with good results in each case. We also report the occurrence of spontaneous corneal perforation in two cases, a complication not previously recognised. The ophthalmic care of these patients must be pursued long-term, as progressive visual impairment may be the most disabling feature of the syndrome.     

Colchicine causes excessive ocular growth and myopia in chicks.

Colchicine has been reported to destroy ganglion cells (GCs) in the retina of hatchling chicks. We tested whether colchicine influences normal ocular growth and form-deprivation myopia, and whether it affects cells other than GCs. Colchicine greatly increased axial length, equatorial diameter, eye weight, and myopic refractive error, while reducing corneal curvature. Colchicine caused DNA fragmentation in many GCs and some amacrine cells and photoreceptors, ultimately leading to the destruction of most GCs and particular sub-sets of amacrine cells. Colchicine-induced ocular growth may result from the destruction of amacrine cells that normally suppress ocular growth, and corneal flattening may result from the destruction of GCs whose central pathway normally plays a role in shaping the cornea.     

Endogenous rhythms in axial length and choroidal thickness in chicks: implications for ocular growth regulation

PURPOSE. To determine whether the diurnal rhythms in axial length and choroidal thickness in the chick eye are endogenous circadian rhythms. METHODS. Six chickens, 14 days of age, were put into darkness for 4 days. Beginning on the 3rd day, ocular dimensions were measured using high-frequency A-scan ultrasonography, in darkness, at 6-hour intervals over 48 hours. Five age-matched chickens reared in a normal light/dark (L/D) cycle and measured at 6-hour intervals for 5 days were controls. RESULTS. The rhythms in axial length and choroidal thickness persist in constant darkness. The phases of these rhythms are approximately in antiphase to one another, similar to those of eyes in a L/D cycle; however, the peak of the rhythm in axial length occurs slightly earlier relative to that of eyes in L/D (12 PM versus 3 PM; P: < 0.05, one-tailed t-test). By the 3rd day in darkness, the rate of growth is significantly higher than that in L/D (117 versus 72 microm/24 hours; P: < 0.01), and the choroid becomes significantly thinner (159 versus 210 microm; P: < 0.0001). CONCLUSIONS. The rhythms in axial length and choroid thickness are circadian rhythms, driven by an endogenous oscillator. The phase of the rhythm in axial length in constant darkness is slightly phase-advanced relative to eyes in L/D and thus is similar to eyes that are deprived of form vision. These findings suggest that in the absence of visual input, the eyes revert to a "default" growth state and that the similarities between the effects of constant darkness and of form deprivation suggest that deprivation may represent a type of "constant" condition.     

可溶性血管内皮生长因子受体-2及其对眼新生血管抑制作用的研究进展

新生血管形成是很多重要眼部疾病的共同病理改变,血管内皮生长因子（vascularendo-thelialgrowthfactor,VEGF）是血管生成重要的促进因子。近年来,可溶性血管内皮生长因子受体-2（solubleVEGFreceptor-2,sVEGFR-2）被证实为一种VEGF促血管生成信号转导通路的天然抑制剂。有研究表明,它与眼部新生血管的发生发展密切相关,可作为新生血管性眼病的抑制因子及其血清标志物而具有临床应用价值。本文就sVEGFR-2在抗眼部新生血管中作用的研究进展予以综述。     

表皮生长因子及其受体在眼表创伤愈合中的作用

表皮生长因子及其受体家族是细胞生长分化的重要调节因素。目前已证实表皮生长因子家族成员可持续表达于泪液中,其受体可表达于眼表上皮,对维持眼表的完整和促进角膜组织的创伤愈合具有重要意义。本文就表皮生长因子及其受体家族在眼表创伤愈合中的作用进行综述。     

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age‐related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis‐dependent pathologies in the eye and non‐ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen‐induced retinopathy, laser‐induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF‐specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research.     

VEGF与眼内血管新生

眼内新生血管是很多眼病致盲的重要原因,例如糖尿病视网膜病变、年龄相关性黄斑变性、早产儿视网膜病变、视网膜中央或分支静脉阻塞、角膜炎和眼外伤等.生长因子中的血管内皮生长因子(vascular endothelial growth factor,VEGF)家族是眼内血管新生的关键因素.在一些眼病中,它通过调控病理性血管发生和增加血管通透性而起作用.本文我们主要阐述眼内新生血管的形成机制和治疗方面的新进展,对VEGF 家族的结构、理化特性、VEGF及受体在眼内血管新生中的作用以及针对血管新生的防治措施进行综述.     

Choroidal thickness and ocular growth in childhood

The involvement of the choroid in ocular growth regulation has been postulated in studies showing that refractive errors correlate with alterations in choroidal thickness (ChT). The advent of optical coherence tomography imaging has enabled qualitative and quantitative assessment of the choroid. In children, ChT changes correlate with a number of ocular pathologies, including myopia, retinopathy of prematurity, and amblyopia. We synthesize mechanisms and evidence regarding choroidal thickness variation during childhood. Subfoveal ChT is influenced by a number of factors including age, ethnicity, gender, axial length, and intraocular pressure. Myopic eyes have thinner choroids compared to emmetropic and hyperopic eyes. ChT may in fact serve as a marker of myopic progression, as ChT thinning occurs early during myopic development, but this association has not been established quantitatively. In addition, subfoveal ChT appears thicker in amblyopic eyes, while prematurity and retinopathy of prematurity may be associated with thinner ChT. Overall, both animal models and clinical research indicate that ChT induces or reflects physiological changes in the eye pertaining to ocular growth or maturation.