LRP2 is a potential molecular target for nonsyndromic pathological myopia

Area of Science:

• Ophthalmology
• Genetics
• Cell Biology

Background:

• High myopia (HM) and posterior staphyloma (PS) are leading causes of global vision impairment.
• Both genetic and environmental factors, including light exposure, contribute to myopia development.

Purpose of the Study:

• To investigate the role of low-density lipoprotein-related receptor type 2 (LRP2) in high myopia and posterior staphyloma.
• To explore the relationship between LRP2, environmental factors, and myopization.

Main Methods:

• Assessed LRP2 levels in vitreous humor from HM/PS patients and human donor eyes.
• Examined LRP2 expression in neural retina and retinal pigment epithelium (RPE) in PS eyes.
• Utilized human induced pluripotent stem cell-derived RPE cells to study LRP2 function via gene silencing.
• Investigated the effect of light exposure and cortisol on LRP2 expression.

Main Results:

• LRP2 levels were decreased in the vitreous of HM and PS patients.
• Reduced LRP2 expression was observed in the neural retina and RPE of PS donor eyes.
• LRP2 silencing in RPE cells altered genes related to eye development, neuronal function, and RPE structure.
• LRP2 expression increased with light exposure (especially red light) but decreased with cortisol treatment.

Conclusions:

• LRP2 is significantly linked to nonsyndromic high myopia and posterior staphyloma.
• Environmental factors like light exposure modulate LRP2 expression, influencing myopization.
• LRP2 represents a potential therapeutic target for treating high myopia.