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Chi-Chao Chan

Publications and source records attributed to Chi-Chao Chan.

At least 19 recordsLinked to original sources
PubMed2007

Molecular pathology of eyes with von Hippel-Lindau (VHL) Disease: a review.

BACKGROUND: von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited systemic cancer syndrome. Recently, many advances have contributed to the understanding of VHL pathophysiology. METHODS: In this article we review recent developments and summarize our findings in VHL molecular pathology related to retinal and optic nerve diseases. RESULTS: Loss of heterozygosity (LOH) within the VHL gene is detected in the stromal cells surrounding the capillary endothelial cells and admixed with glial cells in ocular hemangioblastomas. This finding is in line with similar findings in VHL-associated CNS hemangioblastoma and renal clear cell carcinomas. Increases of vascular endothelial growth factor (VEGF), hypoxia induced factor (HIF), and ubiquitin are found in ocular hemangioblastomas.Interestingly, tumorlet cells, which are composed of poorly differentiated small cells with prominent dark nuclei and little cytoplasm, as well as several stem cell markers, such as erythropoietin (Epo), Epo receptor (EpoR), and CD133, are present in ocular VHL lesions. CXCR4, a CXC chemokine receptor is also expressed in retinal VHL hemangioblastomas. CONCLUSIONS: These findings imply that VHL cells with LOH of the tumor suppressor gene, most likely originate from a hematopoietic/vascular lineage. Targeting these proteins and ischemic factors, not VEGF alone, may be a potential therapeutic approach for VHL-associated ocular hemangioblastomas.

Genes, Tumor Suppressor↗
PubMed2006

Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice.

We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells leads to decreased levels of chondroitin sulfate proteoglycan in the retinal interphotoreceptor matrix. This in turn causes retinal detachment due to the loss of adhesion of the NSR to RPE.

Animals↗
PubMed2006

Pertussis toxin is superior to TLR ligands in enhancing pathogenic autoimmunity, targeted at a neo-self antigen, by triggering robust expansion of Th1 cells and their cytokine production.

Microbial products are assumed to play a major role in triggering pathogenic autoimmunity. Recently accumulated data have shown that these products stimulate the immune system by interacting with TLRs, expressed on APCs. To examine the capacity of various TLR ligands to trigger pathogenic autoimmunity, we used a system in which naive CD4 cells, specific against hen egg lysozyme (HEL), are injected into recipient mice expressing HEL in their eyes. Only when stimulated, the naive cells acquire pathogenic capacity and induce ocular inflammation. Seven TLR ligands were tested in this system: lipoteichoic acid/peptidoglycan, zymosan, poly (I:C), LPS, pertussis toxin (PTX), flagellin, and CpG oligodeoxynucleotide. Treatment of recipient mice with HEL alone stimulated proliferation of the transferred cells, but no disease, whereas ocular inflammation did develop in recipient mice coinjected with HEL and any one of the seven TLR ligands. Inflammation induced by PTX surpassed by its severity those induced by all other tested TLR ligands and was accompanied by a dramatic increase in number of the transferred cells that acquired features of effector Th1 lymphocytes. Ocular inflammation and number of transferred cells in recipients injected with PTX and HEL were substantially reduced by treatment with Abs against IFN-gamma or IL-12, thus indicating the role of these cytokines in the PTX effect. Overall, our observations demonstrate that various TLR ligands are capable of triggering pathogenic autoimmunity and that PTX surpasses other microbial products in this activity, by stimulating excessive proliferation and polarization toward Th1 of naive T cells.

Animals↗
PubMed2006

Eradication of tumor colonization and invasion by a B cell-specific immunotoxin in a murine model for human primary intraocular lymphoma.

Human primary intraocular lymphoma (PIOL) is predominantly a B cell-originated malignant disease with no appropriate animal models and effective therapies available. This study aimed to establish a mouse model to closely mimic human B-cell PIOL and to test the therapeutic potential of a recently developed immunotoxin targeting human B-cell lymphomas. Human B-cell lymphoma cells were intravitreally injected into severe combined immunodeficient mice. The resemblance of this tumor model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and evaluated for molecular markers. The therapeutic effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreally. Results showed that the murine model resembles human PIOL closely. Pathologic examination revealed that the tumor cells initially colonized on the retinal surface, followed by infiltrating through the retinal layers, expanding preferentially in the subretinal space, and eventually penetrating through the retinal pigment epithelium into the choroid. Several putative molecular markers for human PIOL were expressed in vivo in this model. Tumor metastasis into the central nervous system was also observed. A single intravitreal injection of immunotoxin HA22 after the establishment of the PIOL resulted in complete regression of the tumor. This is the first report of a murine model that closely mimics human B-cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL and for the evaluation of new therapeutic approaches. The results of B cell-specific immunotoxin therapy may have clinical implications in treating human PIOL.

Animals↗
PubMed2006

Molecular pathology and CXCR4 expression in surgically excised retinal hemangioblastomas associated with von Hippel-Lindau disease.

PURPOSE: The surgical excision of retinal vascular lesions including hemangioblastomas is rarely practiced. This study investigates the pathological characteristics of 4 patients (3 with von Hippel-Lindau [VHL] disease and 1 with a vasoproliferative retinal tumor) who underwent ocular tumor resection. von Hippel-Lindau is an autosomal dominant disease caused by a defect of the VHL tumor suppressor gene. The VHL protein is required for oxygen-dependent degradation of hypoxia-inducible factor 1alpha. This factor regulates vascular endothelial growth factor (VEGF) and the chemokine receptor CXCR4. Retinal hemangioblastoma is the most common tumor observed in VHL disease. We investigated the expression of CXCR4; its ligand, CXCL12/SDF-1alpha; VEGF; and the VHL gene in VHL disease-associated retinal hemangioblastomas. DESIGN: Interventional case series with immunohistological and molecular pathological analyses. PARTICIPANTS: Immunohistochemistry and molecular pathology of the surgically excised retinal lesions were performed. INTERVENTION: Large retinal hemangioblastomas (1-3 disc diameters) and vasoproliferative tumors were resected surgically after laser photocoagulation in 4 patients. The excised tissues were snap frozen and evaluated by histology. Molecular pathology was performed for the VHL gene, and immunohistochemistry and molecular detection (reverse transcription polymerase chain reaction) were carried out for VEGF, CXCR4, and CXCL12. MAIN OUTCOME MEASURES: Evaluation of clinical presentations and molecular pathology of the excised retinal lesions. RESULTS: Large retinal hemangioblastomas were resected successfully from the 3 VHL cases. Postoperatively, all patients were stable. Molecular analyses disclosed the loss of heterozygosity at the VHL allele locus in the VHL retinal hemangioblastomas but not in the vasoproliferative tumor. High levels of transcript and protein were found for VEGF and CXCR4, whereas low levels of CXCL12 mRNA were expressed in the retinal hemangioblastomas associated with VHL disease. In contrast, very low levels of VEGF and CXCR4 mRNA were detected in the vasoproliferative tumor. Furthermore, increased expression of VEGF and CXCR4 was detected in more active hemangioblastomas. CONCLUSIONS: Surgical resection of large retinal hemangioblastomas may be useful for therapy in selected VHL patients. Activated VHL lesions produce more VEGF. This is the first demonstration of CXCR4 expression in VHL disease-associated retinal hemangioblastomas. We suggest targeting CXCR4 as an additional therapeutic strategy for VHL disease-associated retinal hemangioblastomas.

Adolescent↗
PubMed2006

Inflammatory processes triggered by TCR engagement or by local cytokine expression: differences in profiles of gene expression and infiltrating cell populations.

Immune cell-mediated inflammatory responses are triggered by TCR engagement with the target antigen, the initial event that brings about the complex sequence of events of the inflammatory process. Another form of inflammation is induced by local expression of certain cytokines. Unlike the former form of inflammation, little is known about the basic features of the cytokine-induced responses. Here, we analyzed tissue morphology, the infiltrating cells, and up-regulated, inflammation-related genes in mouse eyes in which inflammation is triggered by local transgenic (Tg) expression of cytokines and compared these features with those in eyes with experimental autoimmune uveitis (EAU), in which inflammation is initiated by engagement of TCR on sensitized T cells with their target antigen, followed by the well-defined, subsequent cytokine production. Eyes of IFN-gamma Tg mice exhibited severe, morphological changes but essentially no inflammation, and intense inflammation was found in eyes of interleukin (IL)-1 or IL-7 Tg mice. The cellular infiltration in eyes of these latter two lines of Tg mice resembled that in eyes with EAU by including many CD4 cells, but unlike in EAU, the infiltration in Tg eyes contained large proportions of B cells and only small numbers of macrophages. Real-time PCR analysis of eye RNA revealed differences among the disease models in the expression profiles of various inflammation-related genes. It is interesting that a bias toward T helper cell type 1 immunity (high IFN-gamma, RANTES/CCL5, MIG/CXCL9, and T-bet but low IL-4, IL-5, and GATA-3 transcripts) was found in EAU eyes but not in eyes of IL-1 and IL-7 Tg mice. The results thus show that similar to TCR engagement, local expression of certain cytokines triggers a complex, subsequent production of numerous inflammation-related molecules, but features of the ensued inflammatory process are determined by the triggering mechanism.

Animals↗
PubMed2006

The level of thymic expression of RPE65 inversely correlates with its capacity to induce experimental autoimmune uveitis (EAU) in different rodent strains.

We have previously shown that immunization with RPE65 produces in rats of four strains a severe inflammatory eye disease, designated experimental autoimmune uveitis (EAU). Here, we examined the uveitogenicity of RPE65 in six strains of mice. Only one strain, C57Bl/6, was found to develop consistently moderate levels of EAU, whereas other strains (BALB/c, B10.A, B10.BR, B10.RIII, C57BL/10J) were found to be essentially resistant to disease induced by RPE65. Analysis of the expression of RPE65 mRNA in thymi of the six mouse strains revealed detectable levels of the transcript in all strains, but with remarkable quantitative differences, with the lowest levels seen in thymi of C57Bl/6 mice, the only strain susceptible to RPE65-induced EAU. Moreover, unlike the finding with the mice, no RPE65 mRNA was detected in thymi of any of the four rat strains (Lewis, BN, F344, SHR) all of which are susceptible to the disease. These data thus indicate that the susceptibility to RPE65-induced EAU is inversely related to the thymic expression of the molecule. The data also suggest that this disease can be induced only in mice in which thymic expression of RPE65 is sufficiently low to allow the escape from deletion of T-cells with the adequate capacity to initiate the pathogenic immune response.

Animals↗
PubMed2006

Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition.

This study investigates age-related macular degeneration (AMD) genetic risk factors through identification of a functional single-nucleotide polymorphism (SNP) and its disease association. We chose ERCC6 because of its roles in the aging process, DNA repair, and ocular degeneration from the gene disruption. Bioinformatics indicated a putative binding-element alteration on the sequence containing C-6530>G SNP in the 5' flanking region of ERCC6 from Sp1 on the C allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift assays displayed distinctive C and G allele-binding patterns to nuclear proteins. Luciferase expression was higher in the vector construct containing the G allele than that containing the C allele. A cohort of 460 advanced AMD cases and 269 age-matched controls was examined along with pathologically diagnosed 57 AMD and 18 age-matched non-AMD archived cases. ERCC6 C-6530>G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6 expression was observed in lymphocytes from healthy donors bearing ERCC6 C-6530>G alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6 C-6530>G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH SNPs may result from biological epistasis, because ERCC6 functions in universal transcription as a component of RNA pol I transcription complex.

5' Flanking Region↗
PubMed2006

Human cytomegalovirus induced cyclooxygenase-2 in human retinal pigment epithelial cells augments viral replication through a prostaglandin pathway.

Cytomegalovirus (CMV) retinitis is characterized by alterations in retinal cell function and host responses to virus replication. The goal of this study was to evaluate the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PGE) in CMV infected human retinal pigment epithelial (RPE) cells and to determine their effect on virus replication. CMV immediate early (IE) protein and COX-2 proteins were identified in RPE cells in retinal tissue sections from patients with CMV retinitis. COX-2 mRNA and protein were induced after CMV infection of human RPE cell cultures. CMV infection of RPE cells induced translocation of NF-kappaB from the cytoplasm to the nucleus. PGE1 and PGE2 were significantly (p<0.001) increased in human RPE cell cultures infected with CMV. Inhibition of CMV IE gene by antisense oligonucleotides abrogated induction of mRNA for COX-2 and protein synthesis of COX-2 and PGE2. PGE enhanced CMV plaque formation and real time PCR analysis revealed that PGE treatment significantly increased CMV DNA copy numbers. These studies demonstrate that when CMV replicates within human RPE cells, COX-2 induction augments virus replication via the PGE pathway. The induction of COX-2 and PGE during retinal CMV infection may augment virus replication and alter a variety of retinal physiological responses.

Cell Nucleus↗
PubMed2006

Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity.

Susceptibility to experimental autoimmune uveitis (EAU), a model for human uveitis induced in mice with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP), is controlled by "natural" CD4+CD25+ regulatory T (T reg) cells. To examine whether endogenous expression of IRBP is necessary to generate these T reg cells, we studied responses of IRBP knockout (KO) versus wild-type (WT) mice. Unexpectedly, not only WT but also IRBP KO mice immunized with a uveitogenic regimen of IRBP in complete Freund's adjuvant (CFA) exhibited CD25+ regulatory cells that could be depleted by PC61 treatment, which suppressed development of uveitogenic effector T cells and decreased immunological responses to IRBP. These EAU-relevant T reg cells were not IRBP specific, as their activity was not present in IRBP KO mice immunized with IRBP in incomplete Freund's adjuvant (IFA), lacking mycobacteria (whereas the same mice exhibited normal T reg cell activity to retinal arrestin in IFA). We propose that mycobacterial components in CFA activate T reg cells of other specificities to inhibit generation of IRBP-specific effector T cells in a bystander fashion, indicating that effective T reg cells can be antigen nonspecific. Our data also provide the first evidence that generation of specific T reg cells to a native autoantigen in a mouse with a diverse T cell repertoire requires a cognate interaction.

Animals↗
PubMed2006

An apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation.

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (E4) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms.

Adult↗
PubMed2006

Detection of Chlamydia pneumoniae in a bilateral orbital mucosa-associated lymphoid tissue lymphoma.

PURPOSE: To detect Chlamydia pneumoniae (C. pneumoniae) gene in a patient with bilateral orbital musoca-associated lymphoid tissue (MALT) lymphoma. DESIGN: Interventional case report. METHODS: A 47-year-old Chinese man with recurrent bilateral orbital masses underwent surgical biopsy. Ophthalmologic and radiographic examinations, routine histology, immunohistochemistry, and molecular analysis for immunoglobulin heavy chain (IgH), bcl-2/IgH gene translocation, and Chlamydia genes were performed. RESULTS: Pathology revealed orbital MALT lymphoma with B-cell monoclonality. In addition to IgH gene rearrangement, C. pneumoniae DNA was detected in the lymphoma. CONCLUSIONS: The finding of C. pneumoniae molecular signatures in this case suggests a possible association of Chlamydia and orbital MALT lymphoma. The infection may contribute to the development of the lymphoma.

Antineoplastic Agents, Alkylating↗
PubMed2006

International Central Nervous System and Ocular Lymphoma Workshop: recommendations for the future.

PURPOSE: To bring together multidisciplinary experts to discuss primary central nervous system lymphoma (PCNSL) and primary intraocular lymphoma (PIOL). METHODS: NIH campus workshop discussion focusing on future work in both clinical and basic lymphoma research. RESULTS: The discussion lead to recommendations on elucidating disease pathobiology, improving diagnostic accuracy and sensitivity, and novel therapeutic strategies. CONCLUSIONS: Approaches which have been successfully applied to other neoplasms, such as microarray, may be applied to improve diagnostic accuracy and sensitivity of PCNSL and PIOL and should be systematically incorporated into clinical trials of both. Development of animal models of PCNSL and PIOL may be useful in understanding the unique ocular and CNS milieu. Disease detection by radiological, nuclear medicine, molecular and flow cytometric approaches should be systematically studied to improve early diagnosis, accurate staging, and response evaluation. Improved therapy remains the ultimate goal. Efforts in these arenas should be coordinated on a national and international level.

Animals↗
PubMed2006

Differential diagnosis of anterior chamber cysts with ultrasound biomicroscopy: ciliary body medulloepithelioma.

PURPOSE: To describe a case with motile cyst in the anterior chamber in the right eye of a 7-year-old boy. METHODS: The right eye's visual acuity was 20/50. Intraocular pressure was 59 mmHg. Slit-lamp examination showed prominent rubeosis iridis and a grey-white mass floating freely in the anterior chamber. Ultrasound biomicroscopy revealed a cystic mass in the anterior chamber. A diagnostic cyclectomy with removal of the anterior chamber cyst was performed. Histopathology of the anterior chamber lesion showed an intact cyst composed of medullary epithelial cells. Medulloepithelioma with malignant criteria was diagnosed and the eye was enucleated. RESULTS: Pathology demonstrated an medulloepithelioma with a few mitotic figures and nuclear pleomorphisms within the ciliary body. The patient was followed for 8 months without any metastasis in the orbit or elsewhere. CONCLUSION: Intraocular medulloepithelioma is a rare embryonic benign or malignant neoplasm typically diagnosed in the first decade of life as a ciliary body mass. A dislodged, free-floating anterior chamber cyst associated with neovascular glaucoma is typical of medulloepithelioma in children. This unique presentation should be differentiated from congenital iris epithelial, post-traumatic, epithelial, parasitic and neoplastic cysts. Ultrasound biomicroscopy is useful for analysing the structure of the anterior segment mass. Ciliary body medulloepithelioma is characterized by echogenic mass heterogeneity and an irregular surface containing multiple cystic cavities. Lack of glial differentiation may predict a better clinical outcome in primary neuroectodermal brain tumours.

Anterior Chamber↗
PubMed2006

Detection of the bcl-2 t(14;18) translocation and proto-oncogene expression in primary intraocular lymphoma.

PURPOSE: Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma that initially infiltrates the retina, vitreous, or optic nerve head, with or without central nervous system involvement. This study examined the expression of the bcl-2 t(14;18) translocation, the bcl-10 gene, and high expression of bcl-6 mRNA in PIOL cells. METHODS: Microdissection and PCR analysis were used to examine vitreous specimens in patients with PIOL for the presence of bcl-2 t(14;18) translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A medical record review was also conducted to determine whether the bcl-2 t(14;18) translocation correlated with prognosis. RESULTS: Forty of 72 (55%) PIOL patients expressed the bcl-2 t(14;18) translocation at the major breakpoint region. Fifteen of 68 (22%) patients expressed the translocation at the minor cluster region. The bcl-10 gene was detected in 6 of 26 (23%) patients, whereas 4 of 4 (100%) PIOL patients expressed higher levels of bcl-6 mRNA compared with inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL patients revealed no significant association between bcl-2 t(14;18) translocations and survival or relapse. However, patients with the translocation were significantly younger. CONCLUSIONS: PIOL has unique molecular patterns of bcl-2, bcl-10, and bcl-6 when compared with other systemic lymphomas. This study lays the foundation for future studies aimed at exploring the genotypic classification of PIOL based on the quantitative molecular framework of gene expression profiling, with the goal of providing useful adjuncts to the pathologic diagnosis of this complex disease.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Mycobacterium-related ocular inflammatory disease: diagnosis and management.

INTRODUCTION: Worldwide, there are approximately 8 million new cases and 3 million deaths from tuberculosis (TB) each year. TB affects the entire body and the eye. Although ocular TB is considered rare, its incidence has varied widely across time, patient populations, and geography. We report 2 patients with unique presentations of ocular TB and detail the treatment and outcome of the disease. MATERIALS AND METHODS: Two cases of ocular inflammation, one with a medical history of systemic TB and the other, with that of presumed systemic TB, were examined. Choroidal granuloma developed in one, and scleritis developed in the other. The literature on ocular TB was comprehensively reviewed. RESULTS: Both patients were diagnosed with ocular TB. The histology of the systemic TB lesions was also illustrated. They responded to aggressive anti- TB and anti-inflammatory therapies. CONCLUSIONS: The diagnosis and management of ocular TB can pose a significant challenge. Physicians and ophthalmologists must include TB among the differential diagnoses of patients with ocular inflammatory diseases and treat ocular TB with a combination of anti-TB and immunosuppressive medications as needed. Immunosuppressive medications applied in this setting must be cautioned and only prescribed by ophthalmologists who are familiar with these agents.

Adult↗
PubMed2005

Exacerbation of retinal degeneration and choroidal neovascularization induced by subretinal injection of Matrigel in CCL2/MCP-1-deficient mice.

This study presents a mouse model for human age-related macular degeneration (AMD) as characterized by subretinal deposit and choroidal neovascularization. Matrigel, a basement membrane extract, solidifies after implantation in tissue and can stimulate local angiogenesis. This study demonstrates the induction of neovascularization and focal retinal degeneration following subretinal Matrigel injection in mice. In senescent mice, the normal functioning of CC chemokine CCL2/MCP-1 and its receptor CCR2 confers protection against age-related retinal degeneration, a disease that shares many similar features with human AMD. Our data shows that CCL2-deficient mice develop more severe disease as compared to the wild-type controls. These findings suggest that Matrigel subretinal injection could be used to generate AMD-like pathological changes. The data support the previously proposed role of CCL2 in AMD pathogenesis.

Animals↗