Amyloid beta deposition related retinal pigment epithelium cell impairment and subretinal microglia activation in aged APPswePS1 transgenic mice

AIM：To identify the pathological role of amyloid beta（Aβ） deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells（RPE） layer and the associated structural and functional changes in Alzheimer＇s disease transgenic mice.METHODS：RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic（NTG） mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin（H＆E） staining and transmission electron microscopy（TEM） examination,whereas the expression of amyloid precursor protein（APP）,Aβ,Zonula occludens-1（ZO-1） and Ionized calcium binding adaptor molecule-1（IBA-1） were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS：In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch＇s membrane（Br M） complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION：The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.

Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance

The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.

For your eyes only:Harnessing human embryonic stem cell-derived retinal pigment epithelial cells to improve impaired vision

Vision loss or impairment resulting from the degeneration of the retinal pigment epithelium and photoreceptor death affects millions worldwide.Recent exciting results from clinical studies of small numbers of patients treated with human embryonic stem cell-derived retinal pigment epithelial cells may provide hope for affected individuals.

Stargardt′s病的临床观察(附69例报道)

目的 :探讨Stargardt′s病的临床表现。方法 :回顾性分析 69例 13 8眼Stargardt′s病的临床和眼底荧光素血管造影 (fundusfluoresceinangiographyFFA)资料 ,分析其视力损害程度、年龄分布状态及病灶表现形态。结果 :视力 0 0 2～ 0 1者 115眼 (83 3 3 % ) ,0 2～ 0 5者 2 3眼 (16 66% ) ;近视力最高Jr =2、最低Jr =0。其中 10岁前起病者3 3例、 11～ 2 0岁起病者 2 6例、 2 1～ 3 0岁起病 4例、 3 1～ 40岁起病 6例。病灶形态 :①单纯黄斑病灶型 2 4例 48眼 ;②黄斑病灶联合眼底黄色斑点型 2 9例 5 4眼 ;③黄斑病灶与后极部色素脱失相融合型 16例 3 2眼。第三型病灶形态与前两型病灶在起病年龄与病程长短方面差别无明显意义 (P >0 0 5 )。三种病灶形态的病变程度差别亦无意义 (P >0 0 5 )。结论 :①Stargardt′s病对视力的影响较大 ,但暂未见到视力全部丧失的病人 ;②Stargardt′s病主要出现于青少年时期 ,亦可在成年人后期发病 ;③黄斑病灶与后极部色素脱失融合为一体的特殊病灶可能是Stargardt′s病的另一种特殊的FFA变异形态。

微囊化人视网膜色素上皮细胞移植治疗帕金森病的实验研究

目的观察微囊化人视网膜色素上皮（RPE）细胞移植治疗帕金森病（PD）大鼠的疗效。方法采用机械分离法和酶消化法原代培养人RPE细胞，传代后用高压静电微胶囊成型装置制作海藻酸钠-多聚赖氨酸-海藻酸钠微囊化细胞．将其立体定向移植人6-羟基多巴胺（6-OHDA）所致的PD模型大鼠的右侧纹状体。实验分为模型组、裸细胞（RPE）组、空囊对照（APA）组以及微囊化细胞（APA—RPE）组。检测各组大鼠移植前后阿朴吗啡诱导的旋转行为变化和移植后8周纹状体中多巴胺fDA）的含量。结果APA—RPE组大鼠在移植后4周阿朴吗啡诱发的旋转次数[（6．25±1．04）r／min]开始减少，与移植前[（12．88±7．34）r／min]相比减少幅度为51．48％，至第8周[（5．87±2．03）dmin]减少更加明显，减少幅度为54．43％，差异均有统计学意义（P〈0．05）；与模型组[（108．14±1．89）mol／L]比较，APA—RPE组移植后8周[（342．63±28．32）mol／L]大鼠纹状体DA含量明显增加，差异有统计学意义（P〈0．05），而RPE组和APA组未见明显变化。结论微囊化人RPE细胞对PD大鼠模型有治疗作用，可作为一种前景良好的治疗PD的方法进一步研究。