Foveal Damage Due to Subfoveal Hemorrhage Associated with Branch Retinal Vein Occlusion

To investigate the functional and morphologic prognoses of eyes with subfoveal hemorrhage from acute branch retinal vein occlusion (BRVO), and to examine the effect of intravitreal ranibizumab injection (IVR) on these prognoses, we assessed 81 eyes with acute BRVO, of which 38 did not receive IVR [IVR(-) group], and 43 were treated with IVR [IVR(+) group] for macular edema. The foveal morphologic changes were examined via optical coherence tomography (OCT). At initial examination, 63 eyes exhibited subfoveal hemorrhage. At final examination, the defect lengths in the foveal external limiting membrane (ELM) and ellipsoid lines in these eyes were longer, and final VA was significantly poorer, compared with eyes without subfoveal hemorrhage. In comparisons between the final measurements in eyes with subfoveal hemorrhage in the IVR(-) and IVR(+) groups, while there were no differences in initial ocular conditions, final VA was significantly better in the IVR(+) group. The defects in the ELM and ellipsoid lines in the IVR(+) group were shorter than those of the IVR(-) group (p = 0.002 in both). Final VA was correlated with the defect lengths of foveal ELM and ellipsoid lines in both the IVR(-) and IVR(+) groups (both p < 0.001). In addition, the defect lengths of foveal ELM and ellipsoid lines were closely correlated with the duration of subfoveal hemorrhage (both p < 0.001). BRVO-associated subfoveal hemorrhage caused damage to the foveal photoreceptors, and visual dysfunction. However, IVR improved these prognoses, by accelerating the absorption of the subfoveal hemorrhage.     

小鼠慢性高眼压模型下视网膜神经节细胞的损伤

目的:通过巩膜外静脉烧烙术建立慢性高眼压模型,研究小鼠慢性高眼压状态下视网膜神经节细胞的凋亡情况.方法:取C57BL/6J小鼠30只.3只作为空白对照组,其余27只右眼为实验眼,左眼为对照眼.术前用iCare眼压计测量眼压,按巩膜外静脉烧烙法建立慢性高眼压模型,术后用iCare眼压计每日监测眼压.分剐取空白对照组6眼,术后1w、4 w造模成功的小鼠各8只16眼眼球,石蜡切片行Tunel法,荧光显微镜下采集图像.小鼠眼压的组间比较采用t检验.结果:给予巩膜外静脉烧烙术后1d、1w、4w小鼠慢性高眼压眼眼压(11.15±0.98、10.65±0.95、10.35±1.05)与对照眼(6.40±0.95、6.35±1.05、6.50±1.15)相比,差异有统计学意义(t=10.77～18.08,P＜0.001).Tunel法结果显示,正常小鼠空白对照组未见明显凋亡的视网膜神经节细胞.慢性高眼压组术后1w、4w可见Tunel阳性表达.而对照组术后1w及4w均未见Tunel阳性表达.结论:巩膜外静脉烧灼法能诱导出持续的肯定的小鼠慢性高眼压模型,慢性高眼压状态下小鼠视网膜神经节细胞发生凋亡,细胞凋亡是小鼠慢性高眼压状态下视网膜神经节细胞损伤的主要方式.     

Retinal degeneration from oxidative damage

Paraquat, a herbicide that generates reactive oxygen species, has been used to probe the oxidative defense systems of lung. In this study, we investigated the effects of paraquat in the retina. There was no significant decline in electroretinogram (ERG) a- or b-wave amplitudes after intravitreous injection of 1 mul of 0.5 mM paraquat in C57BL/6 mice, but loss of ERG function occurred after injection of 0.75 or 1 mM paraquat. Histology in paraquat-injected eyes showed condensation of chromatin and thinning of the inner and outer nuclear layers indicating cell death, and terminal deoxynucleotidyl transferase-mediated duTP-biotinide end labeling demonstrated that one mechanism of cell death was apoptosis. Fluorescence in the retina and retinal pigmented epithelium after intraocular injection of paraquat followed by perfusion with hydroethidine indicated high levels of superoxide radicals, and oxidative damage was demonstrated by staining for acrolein and enzyme-linked immunosorbent assay for carbonyl adducts. Paraquat-induced damage to the outer nuclear layer was greater in BALB/c mice than in C57BL/6 mice, suggesting strain differences in the oxidative defense system of photoreceptors and/or other modifier genes. Intravitreous injection of paraquat provides a new model of oxidative damage-induced retinal degeneration that is likely to be useful for testing new antioxidant treatments.     

A Novel Light Damage Paradigm for Use in Retinal Regeneration Studies in Adult Zebrafish

Light-induced retinal degeneration (LIRD) is commonly used in both rodents and zebrafish to damage rod and cone photoreceptors. In adult zebrafish, photoreceptor degeneration triggers Müller glial cells to re-enter the cell cycle and produce transient-amplifying progenitors. These progenitors continue to proliferate as they migrate to the damaged area, where they ultimately give rise to new photoreceptors. Currently, there are two widely-used LIRD paradigms, each of which results in varying degrees of photoreceptor loss and corresponding differences in the regeneration response. As more genetic and pharmacological tools are available to test the role of individual genes of interest during regeneration, there is a need to develop a robust LIRD paradigm. Here we describe a LIRD protocol that results in widespread and consistent loss of both rod and cone photoreceptors in which we have combined the use of two previously established LIRD techniques. Furthermore, this protocol can be extended for use in pigmented animals, which eliminates the need to maintain transgenic lines of interest on the albino background for LIRD studies.     

Optical Coherence Tomography Reveals Distinct Patterns of Retinal Damage in Neuromyelitis Optica and Multiple Sclerosis

Background

Neuromyelitis optica (NMO) and relapsing-remitting multiple sclerosis (RRMS) are difficult to differentiate solely on clinical grounds. Optical coherence tomography (OCT) studies investigating retinal changes in both diseases focused primarily on the retinal nerve fiber layer (RNFL) while rare data are available on deeper intra-retinal layers.

Objective

To detect different patterns of intra-retinal layer alterations in patients with NMO spectrum disorders (NMOSD) and RRMS with focus on the influence of a previous optic neuritis (ON).

Methods

We applied spectral-domain OCT in eyes of NMOSD patients and compared them to matched RRMS patients and healthy controls (HC). Semi-automatic intra-retinal layer segmentation was used to quantify intra-retinal layer thicknesses. In a subgroup low contrast visual acuity (LCVA) was assessed.

Results

NMOSD-, MS- and HC-groups, each comprising 17 subjects, were included in analysis. RNFL thickness was more severely reduced in NMOSD compared to MS following ON. In MS-ON eyes, RNFL thinning showed a clear temporal preponderance, whereas in NMOSD-ON eyes RNFL was more evenly reduced, resulting in a significantly lower ratio of the nasal versus temporal RNFL thickness. In comparison to HC, ganglion cell layer thickness was stronger reduced in NMOSD-ON than in MS-ON, accompanied by a more severe impairment of LCVA. The inner nuclear layer and the outer retinal layers were thicker in NMOSD-ON patients compared to NMOSD without ON and HC eyes while these differences were primarily driven by microcystic macular edema.

Conclusion

Our study supports previous findings that ON in NMOSD leads to more pronounced retinal thinning and visual function impairment than in RRMS. The different retinal damage patterns in NMOSD versus RRMS support the current notion of distinct pathomechanisms of both conditions. However, OCT is still insufficient to help with the clinically relevant differentiation of both conditions in an individual patient.     

An Isolated Retinal Preparation to Record Light Response from Genetically Labeled Retinal Ganglion Cells

The first steps in vertebrate vision take place when light stimulates the rod and cone photoreceptors of the retina ¹. This information is then segregated into what are known as the ON and OFF pathways. The photoreceptors signal light information to the bipolar cells (BCs), which depolarize in response to increases (On BCs) or decreases (Off BCs) in light intensity. This segregation of light information is maintained at the level of the retinal ganglion cells (RGCs), which have dendrites stratifying in either the Off sublamina of the inner plexiform layer (IPL), where they receive direct excitatory input from Off BCs, or stratifying in the On sublamina of the IPL, where they receive direct excitatory input from On BCs. This segregation of information regarding increases or decreases in illumination (the On and Off pathways) is conserved and signaled to the brain in parallel.The RGCs are the output cells of the retina, and are thus an important cell to study in order to understand how light information is signaled to visual nuclei in the brain. Advances in mouse genetics over recent decades have resulted in a variety of fluorescent reporter mouse lines where specific RGC populations are labeled with a fluorescent protein to allow for identification of RGC subtypes ^{2 3 4} and specific targeting for electrophysiological recording. Here, we present a method for recording light responses from fluorescently labeled ganglion cells in an intact, isolated retinal preparation. This isolated retinal preparation allows for recordings from RGCs where the dendritic arbor is intact and the inputs across the entire RGC dendritic arbor are preserved. This method is applicable across a variety of ganglion cell subtypes and is amenable to a wide variety of single-cell physiological techniques.Download video file.^{(77M, mov)}     

抗VEGF药物联合532 激光治疗视网膜中央静脉阻塞的疗效分析

目的:探讨抗VEGF药物联合532激光治疗视网膜中央静脉阻塞的疗效。方法:选取60例患视网膜中央静脉阻塞患者,年龄38-65岁,研究组(31例)采用抗VEGF药物联合532激光治疗,对照组(29例)单纯给予激光治疗。监测患者治疗前,治疗后3个月的视力,黄斑中心凹厚度(Central macular thickness,CMT)以及治疗后3个月的治疗结果,对联合治疗与单纯激光方式的疗效进行对比。结果:治疗后3个月,研究组有效率明显高于对照组(P0.05)。与治疗前相比,研究组治疗后3个月,视力改善情况较明显(P0.05),且改善幅度大于对照组(P0.05)。对照组治疗后3个月,视力有了小幅度改善,然而与治疗前相比,差异没有统计学意义(P0.05)。治疗前,两组CMT相比,差异没有统计学意义(P0.05)。治疗后3个月,两组CMT均有明显改善,且研究组改变情况优于对照组(P0.05)。所有患者在治疗后3个月内均未严重并发症。结论:抗VEGF药物联合532激光治疗视网膜中央静脉阻塞,可以显著提高患者视力和治疗有效率,降低黄斑水肿,新生血管等并发症发生率,并且不会引起其他并发症。