Tp53 Arg72Pro polymorphism is associated with the expression of apoptosis-related genes in the human retina after retinal detachment

Abstract

Purpose : Identification of mechanisms that prevent retinal detachment (RD)–associated photoreceptor cell loss is essential. It is known that the host's genetic variability, including the presence of genetic polymorphisms in genes involved in apoptosis, serves a crucial role in the functional prognosis of these patients. The present hospital-based prospective cohort study aimed to evaluate the influence of Tp53 Arg72Pro (rs1042522) polymorphism in the inflammation and apoptosis-related genes retinal expression and their impact on the clinical outcomes after successful RD surgery.

Methods : The research was approved by Valladolid Ethics Committee (Ref.1932/A/19). 20 patients who underwent RD surgery have been included so far. 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 retina tissue was performed using PureLink RNA Mini Kit. For mRNA expression analysis, cDNA was synthesised 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 and inflammation-related genes. The patients underwent regular complete ophthalmologic examinations. Statistical analyses were performed using IBM SPSS Statistics v.25.

Results : The results showed that there were no statistical differences in the relative expression of inflammation-related genes according to p.Arg72Pro Tp53 polymorphism distribution. In addition, we showed that being a carrier of Arg/Arg variant for p.Arg72Pro Tp53 polymorphism was associated with an increase in the relative expression of BAX, CASP3and CASP9 apoptosis-related genes in retina human tissue after RD. However, until now, patients carrying the Pro variant showed worse anatomical and functional outcomes after surgery when compared with patients with Arg/Arg genotype.

Conclusions : Retinal cellular apoptosis, after RD, could be associated with the Arg/Arg variant of p.Arg72Pro Tp53 polymorphism. If these results are confirmed it could be a genetic biomarker for RD prognosis.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.