Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium

Rizzolo, Lawrence J.; Peng, Shaomin; Luo, Yan; Xiao, Wei

doi:10.1016/j.preteyeres.2011.06.002

Cited by 150 publications

(131 citation statements)

References 271 publications

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“…39 Disintegration and dysfunction of RPE cells decreases absorption of fluid from the subretinal space and may lead to enhanced diffusion of proteins across the paracellular space from the choriocapillaris into the subretinal space. 40 Notably, similar findings were recently observed in an SI-induced model in which higher doses and the IV administration mode were used and were also observed when mRNA levels were assessed. 15 Previous studies in rabbits exposed to SI, using horseradish peroxidase as a tracer in one study and assessing leakage of gadolinium diethylenetriamine pentaacetic acid using MRI in another, also showed that there is marked breakdown of the diffusion barrier normally maintained by the RPE.…”

Section: Discussionsupporting

confidence: 77%

Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice

Chowers

Cohen

Marks-Ohana

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To characterize the course of sodium iodate (SI)-induced retinal degeneration in young adult albino and pigmented mice. (25, 50, and 100 mg/kg) were performed in 7-to 8-week-old BALB/c and C57Bl/6J mice. Retinal function and structure was assessed at baseline, 24 hours, 3 days, 1, 2, 3, and 4 weeks postinjection by optokinetic tracking response, ERG, optical coherence tomography (OCT), and histologic and immunohistochemical techniques. METHODS. Single intraperitoneal (IP) injections of SI RESULTS.The 50 mg/kg SI dosage was selected after dose ranging due to consistent retinal effects and lack of systemic toxicity. Time-dependent deterioration in retinal function and morphology was consistently observed between 1 and 4 weeks in all measured parameters. These include reduction of ERG responses, thinning of retinal layers as observed by OCT and histology, and loss of RPE nuclei. Immunohistochemistry revealed rapid RPE disorganization with loss of tight junctions and markedly reduced expression of RPE65 and rod opsin, accompanied by mislocalization of cone opsins. Earlier time points displayed variable results, including partial recovery of visual acuity at 1 week and supranormal ERG cone responses at 24 hours, suggesting possible limitations of early intervention and assessment in the SI model. CONCLUSIONS.A single IP injection of 50 mg/kg SI leads to severe RPE injury followed by vision impairment, dysfunction, and loss of photoreceptors in both BALB/c and C57Bl/6J mice. This easily induced and reproducible noninherited model may serve as a useful tool for seeking and evaluating novel therapeutic modalities for the treatment of retinal degenerations caused by primary failure of the RPE.Keywords: sodium iodate, RPE toxicity, retinal degeneration, mouse model D iseases such as AMD, Best disease, and subtypes of retinitis pigmentosa RP are major causes of visual disability. 1 In these diseases, primary dysfunction, degeneration, and loss of the RPE ultimately results in secondary death of photoreceptors, leading to visual loss. [2][3][4] Despite certain progress in the treatment of retinal degeneration, it remains an essentially irreversible process in which many patients eventually lose their sight. Animal models provide an invaluable tool for searching and testing of novel therapeutic modalities. Animals carrying natural mutations (usually in one gene) provide well-established models for inherited retinal diseases. 5,6 However, the pathogenesis of multifactorial retinal degenerations such as AMD involves complex genetic and environmental factors, leading to expression of disease at older ages. 7 The majority of geneticallyinherited animal models of ocular disease do not entirely mimic such conditions because of early disease onset and progression. 8 Regardless of etiology, maintaining proper RPE function is a major therapeutic target in these diseases, and currently pharmaceutical, genetic, and cellular approaches are being tested to this end in a variety of in vitro and in vivo models, as well as in clini...

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Section: Discussionsupporting

confidence: 77%

Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice

Chowers

Cohen

Marks-Ohana

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Several claudins are expressed in human cornea and retina (26,27). Claudin-19 is the prominent claudin expressed in fetal retinal pigment epithelium, and in minor proportion, claudin-3 is expressed; claudin-16 expression in this epithelium seems to be extremely low.…”

Section: Discussionmentioning

confidence: 99%

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Godron¹,

Harambat²,

Boccio³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal tubular disease. It is caused by mutations in CLDN16 and CLDN19, encoding claudin-16 and -19, respectively. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is usually complicated by progressive CKD. The objectives of this study were to describe the clinical and genetic features of familial hypomagnesemia with hypercalciuria and nephrocalcinosis and analyze phenotype-genotype associations in patients with CLDN16 or CLDN19 mutations.Design, setting, participants, & measurements Data from 32 genetically confirmed patients (9 patients with CLDN16 and 23 patients with CLDN19 mutations) from 26 unrelated families were retrospectively reviewed.Results Diagnosis was based on clinical criteria at a median age of 9.5 years and confirmed by genetic testing at a median age of 15.5 years. In total, 13 CLDN16 or CLDN19 mutations were identified, including 8 novel mutations. A founder effect was detected for the recurrent CLDN16 p.Ala139Val mutation in North African families and the CLDN19 p.Gly20Asp mutation in Spanish and French families. CKD was more frequently observed in patients with CLDN19 mutations: survival without CKD or ESRD was 56% at 20 years of age in CLDN19 versus 100% in CLDN16 mutations (log rank P,0.01). Ocular abnormalities were observed in 91% of patients with CLDN19 mutations and none of the patients with CLDN16 mutations (P,0.01). Treatments seem to have no effect on hypercalciuria and CKD progression.Conclusions Patients with CLDN19 mutations may display more severe renal impairment than patients with CLDN16 mutations. Ocular abnormalities were observed only in patients with CLDN19 mutations.

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“…The tight junction is mainly formed by transmembrane proteins, including claudins, occludins, and JAMs, and intracellular ZO scaffolding proteins. In the RPE, the expression of claudins-1, 2, and 5 has been detected in the embryogenesis of chick retinal pigment epithelium (49,50). It has been reported that treatment with HIV-1 gp120 down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin 1-5, leading to increased permeability of the monolayer formed by human RPE cells, and thus allowed translocation of HIV-1 and bacteria across the epithelium (31).…”

Section: Journal Of Biological Chemistry 22983mentioning

confidence: 99%

HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability

Qian

Jiang

et al. 2016

Journal of Biological Chemistry

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Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstances, vascular endothelium and retinal pigment epithelium (RPE), which possess a well developed tight junction complex, form the bloodretinal barrier (BRB) to prevent pathogen invasion. We hypothesize that disruption of the BRB allows pathogen entry into ocular sites. The hypothesis was tested using in vitro models. We discovered that human RPE cells could bind to either HIV-1 gp120 glycoproteins or HIV-1 viral particles. Furthermore, the binding was mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expressed on RPE cells. Upon gp120 binding to DC-SIGN, cellular NF-B signaling was triggered, leading to the induction of matrix metalloproteinases, which subsequently degraded tight junction proteins and disrupted the BRB integrity. DC-SIGN knockdown or prior blocking with a specific antibody abolished gp120-induced matrix metalloproteinase expression and reduced the degradation of tight junction proteins. This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens.

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Integration of tight junctions and claudins with the barrier functions of the retinal pigment epithelium

Cited by 150 publications

References 271 publications

Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice

Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability

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