Advances in the retinal regulation mechanism of form-deprivation myopia北大核心

形觉剥夺性近视(FDM)是由于视网膜接收不到清晰的物像,从而导致眼轴异常伸长,进而诱导近视发生。由于上睑下垂、先天性白内障、角膜混浊和玻璃体积血等原因导致的形觉剥夺引发的近视,其机制可能与在动物模型上观察到的FDM的机制类似。动物模型的研究已经证明了眼部生长和屈光发育的视觉引导以及视网膜调控的存在。视网膜是首先感知异常视觉信号的组织,探讨FDM发生发展机制的关键在于阐明异常的视觉信号输入如何被视网膜所感知并产生相应的生理病理改变。目前的研究已经确定了如多巴胺、视黄酸、血管活性肠肽、黑视蛋白等视网膜神经递质以及视网膜离子外排机制的重要作用。基因组学、蛋白质组学、代谢组学等技术发展使得从宏观层面了解形觉剥夺时视网膜发生的整体改变成为可能,为进一步探究FDM的视网膜调控机制提供了重要的数据支持。     

Methylglyoxal induces hyperpermeability of the blood–retinal barrier via the loss of tight junction proteins and the activation of matrix metalloproteinases

Background  

One of the early signs of diabetic retinopathy is the alteration of the blood–retinal barrier (BRB), which may involve the breakdown of endothelial cell tight junctions. Methylglyoxal (MGO) is a cytotoxic metabolite that is produced from glycolysis in vivo. Elevated levels of MGO are observed in a number of pathological conditions, including neurodegenerative disorders and diabetic complications. Herein, we hypothesize that increased levels of MGO disrupt the tight junction protein known as occludin protein by matrix metalloproteinases (MMPs), leading to breakage of the BRB.     

Can the theory of "whitening" explain the center-surround properties of retinal ganglion cell receptive fields?

To account for the spatial and temporal response properties of the retina, a number of studies have proposed that these properties serve to "whiten" the visual input. In particular, it has been argued that the sensitivity of retinal ganglion cells is matched to the spatial frequency spectrum of natural scenes, resulting in a flattened or "whitened" response spectrum across a range of frequencies. However, we argue that there are two distinct hypotheses regarding the flattening of the spectrum. The decorrelation hypothesis proposes that the magnitude of each ganglion cell tuning curve rises with spatial frequency, resulting in a flattened response spectrum for natural scene stimuli. With appropriate sampling, this scheme allows neighboring neurons to be uncorrelated with each other. The response equalization hypothesis proposes that the overall response magnitude of neurons increases with spatial frequency. The proposed goal of this model is to allow neurons with different receptive field sizes to produce the same average response to natural scenes. The response equalization hypothesis proposes an explanation for the relative gain of different ganglion cells and we show that this proposal fits well with published data. We suggest that both hypotheses are important in understanding the tuning and sensitivity of ganglion cells. However, using a simulation, both models are shown to be insufficient to explain the center-surround receptive field organization of ganglion cells. We discuss other factors, including representational sparseness, which could be related to the goals of ganglion cell spatial processing. We suggest three constraints needed to describe the basic linear properties of P-type ganglion cells: decorrelation, response equalization, and a minimal wiring or minimal size constraint.     

Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells

PURPOSE: A decrease in the ability of Müller cells to remove glutamate from the extracellular space may play a critical role in the disruption of glutamate homeostasis that occurs in the diabetic retina. Because this amino acid is toxic to retinal neurons and is likely to exacerbate oxidative stress, elucidation of the mechanisms by which glutamate levels are elevated in diabetes may help in the understanding of the pathogenesis of diabetic retinopathy. This study tested the hypothesis that the function of the glutamate transporter in Müller cells of the diabetic retina is compromised by a mechanism involving oxidation. METHODS: Müller cells were freshly isolated from normal rats and those made diabetic by streptozotocin injection. The activity of the Müller cell glutamate transporter, which is electrogenic, was monitored by the perforated-patch configuration of the patch-clamp technique. RESULTS: Four weeks after the onset of hyperglycemia, a significant dysfunction of the Müller cell glutamate transporter was detected. After 13 weeks of streptozotocin-induced diabetes, the activity of this transporter was decreased by 67%. Consistent with oxidation's causing this dysfunction, exposure to a disulfide-reducing agent rapidly restored the activity of the glutamate transporter in Müller cells of diabetic retinas. CONCLUSIONS: Early in the course of diabetic retinopathy, the function of the glutamate transporter in Müller cells is decreased by a mechanism that is likely to involve oxidation.     

Age-related changes in the basement membrane of the retinal pigment epithelium of Rpe65 −/− and wild-type mice

Purpose To investigate unusual changes in the basal surface of the retinal pigment epithelium (RPE) cell layer in aging Rpe65 –/– and wild-type mice.Methods The retinas of Rpe65 –/– and wild-type mice of different ages—6 weeks and 3, 6, 12–13 and 16 months—were examined by electron microscopy.Results There was an age-related increase in the width of the basement membrane of both Rpe65 –/– and wild-type mice which was associated with loss of basal infoldings of the plasma membrane of the RPE cells and protrusions of basement membrane material deep into the cytoplasm of these cells. These changes were evident at 6 months of age in RPE65 –/– mice and became extensive at 1 year of age. Similar changes occurred in wild-type mice but were less extensive and were only evident after 1 year of age.Conclusions There is an age-dependent abnormality that develops at the basal surface of murine RPE cells, which resembles some of the changes observed in human age-related macular degeneration. These changes occur earlier in life and are more extensive in Rpe65 mutant mice.     

‘Shadow sign' in congenital hypertrophy of the retinal pigment epithelium of young myopic pigmented patients

Purpose

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) may simulate choroidal melanoma in certain cases. We report unique clinical features we have observed in cases of CHRPE in young myopic pigmented patients.

Methods

Patients who were referred for evaluation of a suspicious choroidal lesion and found to have a CHRPE lesion with the clinical appearance of lesion elevation and a subretinal fluid-like ‘shadow sign'' were included. Patient and lesion characteristics were tabulated. Available images, including fundus photography, ultrasonography, optical coherence tomography (OCT), and fluorescein angiography (FA) were reviewed.

Results

Six patients were included. The ‘shadow sign'' was anterior to the CHRPE lesion in all cases. The mean age of the patients was 27.3 years. The ethnicities of the patients were Chinese (n=1), Hispanic (n=3), or African-American (n=2). Five of six patients were myopic.

Conclusions

Although most CHRPE lesions appear flat on ophthalmoscopy, lesions in young myopic patients of pigmented ethnicities may appear elevated with a ‘shadow sign'' due to ‘dark without pressure.'' This new finding may be related to the vitreoretinal interface in young myopic pigmented patients and must be distinguished from true subretinal fluid and lesion thickness, which are often observed in choroidal melanoma.     

Topographic and age-related changes of the retinal epithelium and Bruch’s membrane of rhesus monkeys

Purpose  

To examine structural differences in the retinal pigmented epithelium (RPE) and Bruch’s membrane of rhesus monkeys (Macaca mulatta) as a function of topography and age.     

The management of retinal vein occlusion: is interventional ophthalmology the way forward?

Retinal vein occlusions (RVO) are the second commonest sight threatening vascular disorder. Despite its frequency treatments for RVO are unsatisfactory and include several that have not been tested by large, well designed, prospective, randomised controlled trials. There is also the lack of long term follow up in many of the available small uncontrolled studies, and the timings of interventions are haphazard. This review aims to evaluate the current knowledge relating to the pathogenesis, suggested treatments for the different types of RVO, and their complications. Isovolaemic haemodilution is of limited benefit and should be avoided in patients with concurrent cardiovascular, renal, or pulmonary morbidity. Evidence to date does not support any therapeutic benefit from radial optic neurotomy, optic nerve decompression, or arteriovenous crossing sheathotomy on its own. Vitrectomy combined with intravenous thrombolysis may offer promise for central RVO. Similarly, vitrectomy combined with arteriovenous sheathotomy intravenous tissue plasminogen activator may offer benefits for branch RVO. RVOs occur at significantly high frequency to allow future prospective randomised controlled studies to be conducted to evaluate the role of different therapeutic modalities singly or in combination.     

Sjögren reticular dystrophy of the retinal pigment epithelium: a case report

PURPOSE: To describe the clinical manifestations in a patient with Sj?gren reticular dystrophy of the retinal pigment epithelium, and the evolution of the disease over a 20-year follow-up period. CASE REPORT: A 45-year-old woman with Sj?gren reticular dystrophy of the retinal pigment epithelium was seen for the first time in 1983; the patient underwent 20 years of annual check-ups. RESULTS: Over the follow-up period, fundus photographs, computerized perimetry, electroretinogram, and electro-oculogram findings had either normal or slightly subnormal outcome. CONCLUSIONS: The results confirm that this disease involves only the retinal pigment epithelium and should not be considered a central tapeto-retinal degeneration or late onset retinopathy.     

Intravitreal ranibizumab (Lucentis®) in the treatment of retinal angiomatous proliferation (RAP)

Background  Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. Methods  Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. Results  Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 μm, and decreased significantly to a mean of 224 μm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 μm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. Conclusions  Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.