Descriptive and functional analysis of the IP3R1 receptor in the pathology of retinitis pigmentosa using C3H/HeJ mice model

• Grant number: 20/02035-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2020
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Théo Henrique de Lima Vasconcellos
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The retina tissue is a photosensitive neuroepithelium present in the inner part of the eye, being an important part of the central nervous system (CNS). In the retina, the light conversion into electrochemical information begins in the photoreceptors cells. Alterations in photoreceptors numbers or in its physiology can lead to several visual diseases. One of those diseases is the retinitis pigmentosa (RP), that can lead to total vision loss. This pathology presents thousands of new cases annually, and there are several well-described genes related to it. During its progression, the RP seems to follow the same initial, intermediate and final stages, leading to rod photoreceptor cell death and further massive loss of cones cells. Although the first insult that leads to primary rod cell death is uncertain, some authors have correlated the secondary cone cell death with excess of cytoplasmic and mitochondrial calcium, leading to the condition of excitotoxicity and oxidative stress. In this context, the type 1 inositol-1,4,5-triphosphate receptor (IP3R1), responsible for intracellular calcium homeostasis, could participate in the progression of this pathology. Therefore, the main aim of this present study is to analyze the distribution of the IP3R1 receptor during the disease progression in autosomal recessive C3H/HeJ RP animal model, and to propose intervention in the pathology through the IP3R1 knockdown in specific time-points. With this approach, it is expected that the decrease of IP3R1 will reduce the cell death progression and prevent visual deficits related to photoreceptor cell death. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARINHO, LUCIANA SIMOES RAFAGNIN; CHIARANTIN, GABRIELLY MARIA DENADAI; IKEBARA, JULIANE MIDORI; CARDOSO, DEBORA STERZECK; DE LIMA-VASCONCELLOS, THEO HENRIQUE; HIGA, GUILHERME SHIGUETO VILAR; FERRAZ, MARIANA SACRINI AYRES; DE PASQUALE, ROBERTO; TAKADA, SILVIA HONDA; PAPES, FABIO; et al. The impact of antidepressants on human neurodevelopment: Brain organoids as experimental tools. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 144, p. 10-pg., 2023-03-17. (19/17892-8, 20/16268-6, 20/11451-7, 20/02035-0, 21/11969-9, 20/11667-0, 19/15024-9, 16/17329-3)

MOVIO, MARILIA INES; DE LIMA-VASCONCELLOS, THEO HENRIQUE; DOS SANTOS, GABRIELI BOVI; ECHEVERRY, MARCELA BERMUDEZ; COLOMBO, ELISABETTA; MATTOS, LEONARDO S.; RESENDE, RODRIGO RIBEIRO; KIHARA, ALEXANDRE HIROAKI. Retinal organoids from human-induced pluripotent stem cells: From studying retinal dystrophies to early diagnosis of Alzheimer?s and Parkinson?s disease. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 144, p. 10-pg., 2023-03-17. (21/14227-3, 21/03711-1, 19/17892-8, 20/02035-0, 20/11667-0, 21/11969-9, 17/26388-6)

DA SILVA, VICTOR A.; BOBOTIS, BIANCA C.; CORREIA, FELIPE F.; LIMA-VASCONCELLOS, THEO H.; CHIARANTIN, GABRIELLY M. D.; DE LA VEGA, LAURA; LOMBELLO, CHRISTIANE B.; WILLERTH, STEPHANIE M.; MALMONGE, SONIA M.; PASCHON, VERA; et al. The Impact of Biomaterial Surface Properties on Engineering Neural Tissue for Spinal Cord Regeneration. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 17, p. 25-pg., 2023-09-01. (17/12112-9, 18/06316-3, 18/19300-8, 19/17892-8, 19/18921-1, 20/02035-0, 20/11667-0, 21/11969-9, 19/24406-2)