Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage.

Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage. Abstract Text:

Mariacarmela Allocca,Umberto Di Vicino,Marco Petrillo,Francesca Carlomagno,Luciano Domenici,Alberto Auricchio,Mariacarmela Allocca,Umberto Di Vicino,Marco Petrillo,Francesca Carlomagno,Luciano Domenici,Alberto Auricchio,

PURPOSE: Delivery of glial cell-derived neurotrophic factor (GDNF), either as a recombinant protein or by retinal gene transfer results in photoreceptor (PR) neuroprotection in genetic models of retinitis pigmentosa (RP). The mechanism of GDNF action and its direct targets in the retina remain unknown. The goal of the present study was to test the neuroprotective effect of GDNF from light-induced damage, a commonly used stimulus of PR degeneration, and to determine whether protection occurs directly on PRs. METHODS: Adeno-associated viral vectors (AAV) were developed that expressed either GDNF or a constitutively (RetMen2A) or pharmacologically activated chimeric GDNF receptor (Fv2Ret). Fv2Ret homodimerization and activation are induced by the administration of the small dimerizer drug AP20187. AAV2/2 vectors and the cytomegalovirus (CMV) promoter were used to transduce GDNF in the retina, whereas RetMen2A and Fv2Ret were transduced by AAV2/5 vectors and their expression restricted to PRs by the rhodopsin promoter. In vivo GDNF levels were measured by ELISA, RetMen2A and Fv2Ret expression and activation in vitro and/or in vivo were assessed by Western blot and immunofluorescence analyses. ERG measurements and histologic analyses were performed to assess morphologic and functional rescue, respectively. RESULTS: GDNF gene transfer resulted in sustained protein expression in the eye. In addition, the results confirmed in vivo that PR-restricted activation of Ret signaling occurred after either AAV-mediated expression of RetMen2A or AP20187-dependent Fv2Ret activation. However, this or AAV-mediated GDNF retinal gene transfer did not result in functional or morphologic PR protection from light-induced damage. CONCLUSIONS: The results suggest that the apoptotic pathways responsible for light-induced PR degeneration are not inhibited by GDNF. However, GDNF signaling was shown to be regulated in time and levels in the retina by the AP20187/Fv2Ret system which is therefore available to be tested as gene-based therapeutic strategy in models of PR degeneration responsive to GDNF.

Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage. Publishing Authors By Initials

M Allocca,U Di Vicino,M Petrillo,F Carlomagno,L Domenici,A Auricchio,M Allocca,U Di Vicino,M Petrillo,F Carlomagno,L Domenici,A Auricchio,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Investigative ophthalmology & visual science

VOLUME: 48

Page Numbers: 5199-206

Journal Abbreviation: Invest. Ophthalmol. Vis. Sci.

ISSN: 0146-0404

DAY: 26

MONTH: Nov

YEAR: 2007

Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7703701

Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage.

AFFILIATION: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.

Country: United States

AGENCY: United States NEI

GRANT: 1 R01 EY015136-01

ACRONYM: EY

MEDLINETA: Invest Ophthalmol Vis Sci

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage Related Publications

• AAV-mediated gene transfer for retinal diseases.
• Activity monitoring in heart failure patients with cardiac resynchronization therapy.
• Biochemical, Pathological, and Skeletal Improvement of Mucopolysaccharidosis VI After Gene Transfer to Liver but Not to Muscle.
• Comparison of Brain Natriuretic Peptide Plasma Levels Versus Logistic EuroSCORE in Predicting In-Hospital and Late Postoperative Mortality in Patients Undergoing Aortic Valve Replacement for Symptomatic Aortic Stenosis.
• Constitutive and AP20187-induced Ret activation in photoreceptors does not protect from light-induced damage.
• Coronary Sinus Visualization by 3-dimensional Real-time Echocardiography.
• Filamin A is mutated in X-linked chronic idiopathic intestinal pseudo-obstruction with central nervous system involvement.
• Hormone-dependent nuclear export of estradiol receptor and DNA synthesis in breast cancer cells.
• In vitro effect of alpha-tocopherol on lysophosphatidylcholine-induced lens damage.
• Influence of left atrial and ventricular volumes on the relation between mitral valve annulus and coronary sinus.
• Inhibition of Estradiol Receptor/Src Association and Cell Growth by an Estradiol Receptor {alpha} Tyrosine-Phosphorylated Peptide.
• Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth.
• Integrating signals between cAMP and MAPK pathways in breast cancer.
• Latent and potential coeliac disease.
• Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy.
• Mankind adaptation and present human health.
• Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors.
• Preferential silencing of a common dominant rhodopsin mutation does not inhibit retinal degeneration in a transgenic model.
• Transglutaminase 1 deficiency and corneocyte collapse: an indication for targeted molecular screening in autosomal recessive congenital ichthyosis.
• Versatility of AAV vectors for retinal gene transfer.
• [Not Available.]
• [Not Available.]