Polymorphism in THBS1 gene is associated with post-refractive surgery chronic ocular surface inflammation

Area of Science:

• Ophthalmology
• Genetics
• Immunology

Background:

• Chronic ocular surface inflammation, such as keratoconjunctivitis, can occur after refractive surgery.
• The thrombospondin 1 (THBS1) gene plays a role in tissue remodeling and inflammation.
• Understanding the genetic factors influencing post-refractive surgery inflammation is crucial for patient outcomes.

Purpose of the Study:

• To investigate the association between single nucleotide polymorphisms (SNPs) in the THBS1 gene and the development of chronic keratoconjunctivitis following refractive surgery.
• To explore the relationship between specific THBS1 gene variations, THBS1 protein expression, and inflammatory markers on the ocular surface.

Main Methods:

• A retrospective cohort study was conducted involving 143 active duty U.S. Army soldiers who underwent refractive surgery.
• DNA was extracted from pre-operative conjunctival impression cytology samples for genotyping of five THBS1 SNPs.
• RNA was extracted from post-operative samples for gene expression analysis (real-time PCR) and participants were monitored for 1 year for keratoconjunctivitis development.

Main Results:

• Carriers of minor alleles for three THBS1 SNPs (rs1478604, rs2228262, rs2292305) showed increased susceptibility to chronic keratoconjunctivitis.
• Specifically, carriers of the rs1478604 minor allele had a significantly higher odds ratio for developing the condition.
• These carriers also exhibited reduced thrombospondin 1 (TSP1) levels and increased interleukin-1β (IL-1β) expression in ocular surface epithelial cells.

Conclusions:

• Genetic variations in the THBS1 gene, leading to decreased TSP1 expression, significantly elevate the risk of chronic ocular surface inflammation post-refractive surgery.
• The findings suggest a genetic predisposition to post-refractive surgery inflammation linked to THBS1 gene polymorphisms.
• Further research with larger sample sizes is recommended to validate these findings and explore therapeutic implications.