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Fulltext Post viral acute multifocal posterior placoid pigment epithiopathy in a teenage child

Nga AD, Ramli N, Mimiwati Z

Med J Malaysia, 2009 Jun;64(2):176-8.
PMID: 20058585 MyJurnal

We report a rare case of a young boy presenting with bilateral blurring of vision following a viral like illness. Fundus examination revealed multiple pale cream-coloured lesions scattered across the posterior pole of both eyes. Fundus fluorescein angiography showed characteristic features of early hypofluorescence and late hyperfluorescence, further confirming the diagnosis of acute posterior placoid pigment epitheliopathy (AMPPPE). He was treated with topical steroids for the accompanying mild anterior uveitis. He had a prompt visual recovery with no adverse sequelae.

Matched MeSH terms: Retinal Diseases/drug therapy
Taurine protects against NMDA-induced retinal damage by reducing retinal oxidative stress

Jafri AJA, Agarwal R, Iezhitsa I, Agarwal P, Ismail NM

Amino Acids, 2019 Apr;51(4):641-646.
PMID: 30656415 DOI: 10.1007/s00726-019-02696-4

This study aimed to evaluate effect of TAU on NMDA-induced changes in retinal redox status, retinal cell apoptosis and retinal morphology in Sprague-Dawley rats. Taurine was injected intravitreally as pre-, co- or post-treatment with NMDA and 7 days post-treatment retinae were processed for estimation of oxidative stress, retinal morphology using H&E staining and retinal cell apoptosis using TUNEL staining. Treatment with TAU, particularly pre-treatment, significantly increased retinal glutathione, superoxide dismutase and catalase levels compared to NMDA-treated rats; whereas, the levels of malondialdehyde reduced significantly. Reduction in retinal oxidative stress in TAU pre-treated group was associated with significantly greater fractional thickness of ganglion cell layer within inner retina and retinal cell density in inner retina. TUNEL staining showed significantly reduced apoptotic cell count in TAU pre-treated group compared to NMDA group. It could be concluded that TAU protects against NMDA-induced retinal injury in rats by reducing retinal oxidative stress.

Matched MeSH terms: Retinal Diseases/drug therapy*
Sustained Connexin43 Mimetic Peptide Release From Loaded Nanoparticles Reduces Retinal and Choroidal Photodamage

Mat Nor N, Guo CX, Rupenthal ID, Chen YS, Green CR, Acosta ML

Invest Ophthalmol Vis Sci, 2018 07 02;59(8):3682-3693.
PMID: 30029255 DOI: 10.1167/iovs.17-22829

Purpose: To evaluate the long-term effect on inflammation and inflammasome activation of intravitreally delivered connexin43 mimetic peptide (Cx43MP) in saline or incorporated within nanoparticles (NPs) for the treatment of the light-damaged rat eye.
Methods: Light-induced damage to the retina was created by exposure of adult albino Sprague-Dawley rats to intense light for 24 hours. A single dose of Cx43MP, Cx43MP-NPs, or saline was injected intravitreally at 2 hours after onset of light damage. Fluorescein isothiocyanate (FITC)-labelled Cx43MP-NPs were intravitreally injected to confirm delivery into the retina. Electroretinogram (ERG) recordings were performed at 24 hours, 1 week, and 2 weeks post cessation of light damage. The retinal and choroidal layers were analyzed in vivo using optical coherence tomography (OCT) and immunohistochemistry was performed on harvested tissues using glial fibrillary acidic protein (GFAP), leukocyte common antigen (CD45), and Cx43 antibodies.
Results: FITC was visualized 30 minutes after injection in the ganglion cell layer and in the choroid. Cx43MP and Cx43MP-NP treatments improved a-wave and b-wave function of the ERG compared with saline-injected eyes at 1 week and 2 weeks post treatment, and prevented photoreceptor loss by 2 weeks post treatment. Inflammation was also reduced and this was in parallel with downregulation of Cx43 expression.
Conclusions: The slow release of Cx43MP incorporated into NPs is more effective at treating retinal injury than a single dose of native Cx43MP in solution by reducing inflammation and maintaining both retinal structure and function. This NP preparation has clinical relevance as it reduces possible ocular complications associated with repeated intravitreal injections.

Matched MeSH terms: Retinal Diseases/drug therapy*
Fulltext Connexin Hemichannel Block Using Orally Delivered Tonabersat Improves Outcomes in Animal Models of Retinal Disease

Mat Nor MN, Rupenthal ID, Green CR, Acosta ML

Neurotherapeutics, 2020 Jan;17(1):371-387.
PMID: 31637594 DOI: 10.1007/s13311-019-00786-5

Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2 weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.

Matched MeSH terms: Retinal Diseases/drug therapy*
Fulltext Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases

Mat Nor MN, Rupenthal ID, Green CR, Acosta ML

Int J Mol Sci, 2021 Feb 10;22(4).
PMID: 33578721 DOI: 10.3390/ijms22041755

Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.

Matched MeSH terms: Retinal Diseases/drug therapy*