Modulation of the expression of the transcription factor Max in rat retinal ganglion cells by a recombinant adeno-associated viral vector

Petrs-Silva, Hilda; Chiodo, Vince A.; Chiarini, Luciana B.; Hauswirth, William W.; Linden, Rafael

doi:10.1590/s0100-879x2005000300008

Cited by 5 publications

(14 citation statements)

References 17 publications

(14 reference statements)

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“…Intravitreal injection of rAAV2 vector was performed 2 weeks before retinal explants, as previously described. 43 In 1-day-old (P1) rat pups, hypothermia was used to induce anesthesia. Pups were placed onto a dry rubber glove set on ice for 2 to 3 minutes and then placed onto a clean paper towel under the dissecting scope.…”

Section: Methodsmentioning

confidence: 99%

“…Two weeks after intravitreal injection of rAAV2, at 15 days after birth, retinal explants were prepared as previously described. 43 Rats were euthanized, and the eyeballs were removed and collected in an ice-cold PBS solution containing 1% penicillin. The anterior segment was removed by a sharp incision in the pars plana and cut 360°.…”

Section: Methodsmentioning

confidence: 99%

“… 40 , 41 These data were in line with evidence that selective overexpression of MAX in endothelial cells blocks apoptosis promoted by serum withdrawal 42 and raised the hypothesis that the reduced nuclear content of MAX might be instrumental for the degeneration of the RGCs. Indeed, an ex vivo study of axotomized retinal explants 43 showed that condensed TUNEL-positive nuclei of RGCs did not express MAX, while RGCs overexpressing MAX showed healthy morphology.…”

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confidence: 99%

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Neuroprotective Gene Therapy by Overexpression of the Transcription Factor MAX in Rat Models of Glaucomatous Neurodegeneration

Lani-Louzada

Marra

Dias

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Based on our preview evidence that reduced nuclear content of the transcription factor Myc-associated protein X (MAX) is an early event associated with degeneration of retinal ganglion cells (RGCs), in the present study, our purpose was to test whether the overexpression of human MAX had a neuroprotective effect against RGC injury. Methods Overexpression of either MAX or green fluorescent protein (GFP) in the retina was achieved by intravitreal injections of recombinant adenovirus-associated viruses (rAAVs). Lister Hooded rats were used in three models of RGC degeneration: (1) cultures of retinal explants for 30 hours ex vivo from the eyes of 14-day-old rats that had received intravitreal injections of rAAV2- MAX or the control vector rAAV2- GFP at birth; (2) an optic nerve crush model, in which 1-month-old rats received intravitreal injection of either rAAV2- MAX or rAAV2- GFP and, 4 weeks later, were operated on; and (3) an ocular hypertension (OHT) glaucoma model, in which 1-month-old rats received intravitreal injection of either rAAV2- MAX or rAAV2- GFP and, 4 weeks later, were subject to cauterization of the limbal plexus. Cell death was estimated by detection of pyknotic nuclei and TUNEL technique and correlated with MAX immunocontent in an ex vivo model of retinal explants. MAX expression was detected by quantitative RT-PCR. In the OHT model, survival of RGCs was quantified by retrograde labeling with DiI or immunostaining for BRN3a at 14 days after in vivo injury. Functional integrity of RGCs was analyzed through pattern electroretinography, and damage to the optic nerve was examined in semithin sections. Results In all three models of RGC insult, gene therapy by overexpression of MAX prevented RGC death. Also, ON degeneration and electrophysiologic deficits were prevented in the OHT model. Conclusions Our experiments offer proof of concept for a novel neuroprotective gene therapy for glaucomatous neurodegeneration based on overexpression of MAX.

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“…A localização nuclear de fatores de transcrição é necessária para que ocorram suas ações transcricionais (Muratani e Tansey, 2003 Aumento nos níveis de Max através de sua superexpressão em células endoteliais in vitro foi capaz de bloquear a apoptose induzida pela privação do soro do meio de cultura (Shichiri et al, 1999). O uso de vetor viral recombinante para aumentar a expressão de Max in vivo em células ganglionares, da retina de ratos recém-nascidos, mostrou efeito protetor após a axotomia (Petrs-Silva et al, 2005).…”

Section: Aspectos Molecularesunclassified

“…A morte de células ganglionares da retina é um modelo amplamente aceito de apoptose no SNC mesmo grupo de pesquisadores, em outro trabalho, utilizando um vetor do tipo adenovirus-associado recombinante contendo o gene max, mostrou que esta proteína desempenha um papel protetor em neurônios da retina de ratos. Eles sugeriram que a exclusão (ou degradação) nuclear precoce de Max, em axônios danificados de células ganglionares, poderia ser um passo necessário para a execução da degeneração retrógrada(Petrs-Silva et al, 2005) Bibancos et al, 2007)…”

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Estudo do fator de transcrição Max no hipocampo de camundongos adolescentes submetidos a um modelo de submissão social prolongada.

Amaral¹

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show abstract

Modulation of the expression of the transcription factor Max in rat retinal ganglion cells by a recombinant adeno-associated viral vector

Cited by 5 publications

References 17 publications

Neuroprotective Gene Therapy by Overexpression of the Transcription Factor MAX in Rat Models of Glaucomatous Neurodegeneration

Estudo do fator de transcrição Max no hipocampo de camundongos adolescentes submetidos a um modelo de submissão social prolongada.

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