Macular Degeneration: Liu Y

Ma Z, Han L, Wang C, Dou H, Hu Y, Feng X, Xu Y, Wang Z, Yin Z, Liu Y. · Peking University Eye Center, Peking University Third Hospital, Beijing, Peoples Republic of China. · Invest Ophthalmol Vis Sci. · Pubmed #19117919 No free full text.

Abstract: PURPOSE: To evaluate a surgical procedure for patients with hemorrhagic age-related macular degeneration (AMD). METHODS: This procedure consisted of excision of the choroidal neovascular membrane and transplantation of autologous retinal pigment epithelium (RPE)-Bruch's membrane complex. The RPE-Bruch's membrane complex for transplantation was surgically developed by dissecting Bruch's membrane with the choriocapillaris from the medium size choroidal vessel layer at the midperipheral region of the choroid. Twenty-one eyes of 21 patients had this surgical procedure. Visual function tests included best corrected visual acuity (BCVA), multifocal (mf)ERG, and microperimetry. Optical coherence tomography (OCT), fluorescein angiography, and autofluorescence examinations were performed to study the status of the transplanted graft. RESULTS: Among the 21 eyes, 17 with complete clinical data and qualified follow-up durations, which were 20.35 +/- 10.31 months on average, were analyzed in this series. On the last follow-up visit, the mean for the ETDRS scores increased from 28.65 +/- 23.99 before surgery to 47.76 +/- 17.22 after surgery. Microperimetry showed that after surgery, seven eyes gained central fixation at the 12-month follow-up examination. However, two eyes lost their central fixation on the last follow-up visit. Fourteen (82.35%) of the transplanted patches preserved normal color without depigmentation. Among the 21 eyes, proliferative vitreoretinopathy (PVR) occurred in 3 (14.29%), and a recurrent neovascular membrane was observed in one eye (4.76%). CONCLUSIONS: The transplantation of the autologous RPE-Bruch's membrane complex can increase the visual acuity of patients with hemorrhagic AMD. The surviving transplanted graft with functional overlying retina was observed after surgery.

Tezel TH, Geng L, Lato EB, Schaal S, Liu Y, Dean D, Klein JB, Kaplan HJ. · Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. · Invest Ophthalmol Vis Sci. · Pubmed #19060278 No free full text.

Abstract: PURPOSE: To demonstrate the production of hemoglobin by human retinal pigment epithelium (RPE). METHODS: Proteomic analysis using 10 donor eyes identified hemoglobin as a major constituent of soluble human RPE proteome. Western blot analysis, RT-PCR, and immunocytochemistry were used to confirm the RESULTS: The presence of erythrocyte-specific proteins within primary human RPE cytosol was investigated to rule out phagocytosis as the source of hemoglobin. ELISA was used to determine the rate of hemoglobin secretion from human RPE cells. Globin mRNA expression of human RPE was studied in comparison with a human erythroblast cell line and a spontaneously transformed human RPE cell line (ARPE-19). results. Hemoglobin is a regular constituent of soluble human RPE proteome. RT-PCR and Western blot analysis confirmed the presence of hemoglobin in human RPE. No other erythrocyte-specific proteins were detected within human RPE cytosol. Hemoglobin expression persisted up to seven passages in vitro. Human RPE globin expression exceeded that in human erythroblast and ARPE-19 cells. Immunohistochemistry revealed the presence of hemoglobin within RPE and Bruch's membrane. The hemoglobin release rate was calculated to be 1.9+/-1.2 attomoles per cell per hour. CONCLUSIONS: Hemoglobin expression by human RPE brings a new perspective to the understanding of oxygen transport to the outer retina. Malfunction of RPE-hemoglobin production may underlie the pathophysiology of ocular diseases characterized by subfoveal hypoxia and VEGF upregulation, such as age-related macular degeneration and diabetic retinopathy. Pharmacologic modulations of local hemoglobin production in RPE cells will create new opportunities to interfere with the course of these diseases.

Zhao L, Wang Z, Liu Y, Song Y, Li Y, Laties AM, Wen R. · Department of Ophthalmology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104, USA. · Mol Vis. · Pubmed #17615538 links to  free full text

Abstract: PURPOSE: A cardinal pathological feature of age-related macular degeneration (AMD) is the deposition of extracellular material between the retinal pigment epithelium (RPE) and Bruch's membrane, pathologically described as sub-RPE deposits. Both the presence and local organization of these deposits contribute to the clinical manifestations of AMD, including localized deposits clinically recognized as drusen. The biogenesis of sub-RPE deposits remains elusive. This work explores the pathological processes of sub-RPE deposit formation. METHODS: Matrigel was injected to the subretinal space of rats to create an amorphous deposit. Tissue sections were examined by light or confocal microscopy. RESULTS: In the presence of the subretinal deposit of Matrigel, RPE cells leave Bruch's membrane to migrate toward photoreceptors and then form a new layer between the deposit and photoreceptors, resulting in RPE translocation. The new RPE layer displaces the deposit to the sub-RPE location and therefore it becomes a sub-RPE deposit. The RPE mobilization requires the presence of photoreceptors. Bruch's membrane devoid of RPE attachment becomes vulnerable to invasion by new blood vessels from the choroid. CONCLUSIONS: Our work supports a novel model of sub-RPE deposit formation in which excessive material first accumulates in the subretinal space, disrupting the physical contact between RPE cells and photoreceptors. To restore the contact, RPE cells migrate toward photoreceptors and form a new layer. The subretinal material is consequently displaced to the sub-RPE location and becomes sub-RPE deposit. Our data also provide evidence that the presence of sub-RPE deposit is sufficient to induce choroidal neovascularization to penetrate Bruch's membrane.

Liu Y, Wen F, Huang S, Luo G, Yan H, Sun Z, Wu D. · State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou 510060, People's Republic of China. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17406882 No free full text.

Abstract: PURPOSE: To identify the subtype frequency and clinical features of neovascular age-related macular degeneration (AMD) in Chinese patients. METHODS: From January 2003 to August 2006, we investigated prospectively 155 newly diagnosed patients with presumed neovascular AMD. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed in both eyes of all patients. Subtype frequency and clinical features were recorded according to their angiograms. RESULTS: Three subtypes of lesion were noted, which were polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) and mixed lesions. Of the 155 patients, 105 (67.7%) had choroidal neovascularization (CNV) of the typical type seen in AMD, 38 (24.5%) had PCV and seven (4.5%) had RAP. In five (3.2%) additional cases, mixed lesions were noted. In 38 cases (47 eyes) with PCV, the rates of subfoveal, juxtafoveal and extrafoveal lesion were respectively 29.8% (14 eyes), 8.5% (four eyes), and 61.7% (29 eyes), compared with 75.6%, 14.6% and 9.8% for CNV lesion (P < 0.01). The percentage of subfoveal lesion in PCV group was significantly lower than that in the CNV group (P < 0.01). The location of the RAP lesion was subfoveal in two (28.6%) eyes, juxtafoveal in three (42.9%) eyes and extrafoveal in two (28.6%) eyes. The five eyes with mixed lesions were all PCV coexisting with CNV at the same eye, and in all of the five cases, CNV was subfoveal while PCV was extrafoveal. CONCLUSIONS: In this hospital-based study, PCV accounts for 24.5% of neovascular AMD and is the most common subtype, RAP is less frequent (4.5%), and mixed lesions are much less common in Chinese patients. PCV is least likely to involve the fovea in neovascular AMD.

Howes KA, Liu Y, Dunaief JL, Milam A, Frederick JM, Marks A, Baehr W. · Moran Eye Center, University of Utah Health Science Center, Salt Lake City, UT 84112, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15452081 links to  free full text

Abstract: PURPOSE: Advanced glycation end products (AGE) exacerbate disease progression through two general mechanisms: modifying molecules and forming nondegradable aggregates, thus impairing normal cellular/tissue functions, and altering cellular function directly through receptor-mediated activation. In the present study receptor for AGE (RAGE)-mediated cellular activation was evaluated in the etiology of human retinal aging and disease. METHODS: The maculas of human donor retinas from normal eyes and eyes with early age-related macular degeneration (AMD) and advanced AMD with geographic atrophy (GA) were assayed for AGE and RAGE by immunocytochemistry. Cultured ARPE-19 cells were challenged with known ligands for RAGE, AGE, and S100B, to test for activation capacity. Immunocytochemistry, real-time RT-PCR, immunoblot analysis, and the TUNEL assay were used to determine the consequences of RPE cellular activation. RESULTS: Little to no immunolabeling for AGE or RAGE was found in photoreceptor and RPE cell layers in normal retinas. However, when small drusen were present, AGE and RAGE were identified in the RPE or both the RPE and photoreceptors. In early AMD and GA, the RPE and remnant photoreceptor cells showed intense AGE and RAGE immunolabeling. Both AGE and S100B activated cultured RPE cells, as revealed by upregulated expression of RAGE, NFkappaB nuclear translocation, and apoptotic cell death. CONCLUSIONS: Immunolocalization of RAGE in RPE and photoreceptors coincided with AGE deposits and macular disease in aged, early AMD, and GA retinas. Further, AGE stimulated RAGE-mediated activation of cultured ARPE-19 cells in a dose-dependent fashion. AGE accumulation, as occurs with normal aging and in disease, may induce receptor-mediated activation of RPE/photoreceptor cells, contributing to disease progression in the aging human retinas.

McHenry CL, Liu Y, Feng W, Nair AR, Feathers KL, Ding X, Gal A, Vollrath D, Sieving PA, Thompson DA. · Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15111602 links to  free full text

Abstract: PURPOSE: Mutations in the MERTK gene are responsible for retinal degeneration in the Royal College of Surgeons (RCS) rat and are a cause of human autosomal recessive retinitis pigmentosa (RP). This study reports the identification and functional analysis of novel MERTK mutations to provide information regarding whether they are causative of severe rod-cone degeneration in a young patient. METHODS: MERTK missense variants identified by single-strand conformational polymorphism (SSCP) and sequence analysis were introduced into expression constructs and used to transfect HEK293T cells. Recombinant protein expression was assayed with anti-MERTK and anti-phosphotyrosine antibodies. Protein turnover was assayed in pulse-chase studies of 35S-methionine incorporation. Transcript levels were determined by quantitative RT-PCR. RESULTS: Three MERTK sequence variants were identified in a patient with rod-cone dystrophy: R722X in exon 16 and R865W in exon 19 on the paternal allele and R844C in exon 19 on the maternal allele. The R844C sequence change affects an evolutionarily conserved amino acid residue and was not detected in unaffected individuals. In transfected HEK293Tcells, wild-type (wt) and W865 MERTK were expressed at equivalent levels and present in the plasma membrane, stimulated tyrosine phosphorylation, and induced significant rounding of the cell bodies. In contrast, C844 MERTK was expressed at low levels and did not stimulate tyrosine phosphorylation. In addition, the relative stability of C844 MERTK was significantly less than wt in assays of protein turnover. At age 13, the patient had 20/60 and 20/200 acuities, tunnel vision of 5 degrees centrally, and a far temporal peripheral crescent bilaterally, and ERGs were nondetectable. The fundi showed bull's-eye macular atrophy and widespread RPE thinning. CONCLUSIONS: The present study reports the identification of R844C, the first putative pathogenic MERTK missense mutation that results in severe retinal degeneration with childhood onset when in compound heterozygous form with a R722X allele. The loss of function of C844 MERTK is probably due to decreased protein stability.

Cheng B, Liu Y, Liu X, Ge J, Ling Y, Zheng X. · Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. · Zhonghua Yan Ke Za Zhi. · Pubmed #12133369 No free full text.

Abstract: OBJECTIVE: To investigate the effects of phacoemulsification on the macula following uncomplicated phacoemulsification by optical coherence tomography (OCT). METHODS: Eighty eyes of the senile cataract were chosen randomly. The uncomplicated phacoemulsification was performed. OCT was examined preoperatively and 1 week after the surgery. Preoperative visual acuity, the retinal thickness and phaco power were compared with those after surgery. RESULTS: In 80 eyes, the preoperative mean foveal thickness was (142.9 +/- 16.7) micrometer and the postoperative (157.9 +/- 36.7) micrometer, the difference being not significant (P > 0.05). Three eyes had macular edema 1 week after surgery. In 11 eyes with Tyndall sign (+ +), the mean postoperative foveal thickness was thicker than the mean preoperative value (P < 0.05). In lower phaco power group, the mean postoperative foveal thickness was (156.2 +/- 18.3) micrometer and the higher phaco power group was (172.6 +/- 32.9) microm (P < 0.05). The best corrected visual acuity after surgery had a negative correlation with the retinal thickness. CONCLUSIONS: The retinal thickening and macular edema can be found after uncomplicated phacoemulsification. The higher phaco power results in significant inflammation and thicker retina. The visual consequences were proportional to the degrees of macular thickening.