TP53 Arg72Pro polymorphism as a potential biomarker for functional prognosis in patients with retinal detachment: Insights from real-world clinical data and an experimental mouse model of retinal detachment

Abstract

Purpose : To evaluate the impact of Tp53 Arg72Pro (rs1042522) polymorphism, apoptosis, inflammation and stress response genes on the final clinical outcomes in patients after a successful retinal detachment (RD) surgery and in an experimental RD mouse model.

Methods : Hospital-based prospective cohort design involving 180 patients (so far) who underwent RD surgery and 30 humanized Tp53 Arg72Pro-expressing mice. Genotyping for p.Arg72Pro Tp53 polymorphism was conducted using the PCR-RFLP technique on DNA extracted from peripheral blood. Tp53 exon 4, where BstU1 RFLP is located, was amplified by PCR. Total RNA extraction from human and mouse retinal tissue was performed using PureLink RNA Mini Kit. For mRNA expression analysis, cDNA was synthesized by reverse transcription using a commercial High-Capacity cDNA Reverse Transcription Kit. qPCR was performed using SYBR Green PCR master mix and gene-specific primer sets for apoptosis, stress and inflammation-related genes. The patients underwent a complete ophthalmologic examination. Statistical analyses were performed using IBM SPSS Statistics v.25.

Results : There were statistical differences in the relative expression of glial fibrillary acidic protein (GFAP) and inflammation-related genes according to p.Arg72Pro Tp53polymorphism distribution in mice. In addition, Being a carrier of Arg/Arg variant for p.Arg72Pro Tp53 polymorphism was associated with an increase in the relative expression of BAX, CASP3, andCASP9 apoptosis-related genes in human and mouse retinal tissue after RD. However, patients carrying the Pro variant showed worse anatomical and functional outcomes when the surgery was performed more than 7 days after the initial diagnosis compared with patients with Arg/Arg genotype.

Conclusions : The TP53 Arg72Pro polymorphism may influence the balance between pro- and anti-apoptotic gene expression in the retina after RD. Clinical outcomes and GFAP in mice vary when surgery is performed after 7 days, depending on the p.Arg72Pro Tp53 polymorphism distribution. If these results are confirmed, it could serve as a genetic biomarker for functional prognosis.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Table 1: Study population clinical characteristics so far.

 

Mouse model results: Apoptosis - TUNEL