Chaperone Proteins in Eye Cataract: A Novel Approach for Treatment

Cataracts are a leading cause of visual impairment globally, affecting millions of people worldwide. According to the World Health Organization, cataracts cause more than 40% of blindness cases, and approximately 90% of blindness in developed countries (1). The prevalence of cataracts is around 47.8% among people over 50 years old, with aging, genetics, diseases, drugs, smoking, or UV exposure being common risk factors (2).

The development of cataract pharmacotherapy has been a significant area of research in recent years. Our team has built an optimized platform to screen potential therapeutic agents from lanosterol derivatives and identified novel pharmacological substances that can reverse lens opacity by dissolving the aggregation of crystallin proteins (3). This breakthrough indicates that protein aggregation is not an endpoint and could be reversed with specific small-molecule drugs, significantly boosting the development of the cataract pharmacopeia.

Several anti-cataract drugs have been applied in clinics, but their effectiveness remains unsatisfactory. Anti-cataract drug screening was previously based on specific pathogenic factors such as oxidative stress, excess quinoid substances, and aldose reductase (AR) activation. However, the development of chaperone proteins as a therapeutic approach has shown promising results.

Chaperone proteins play a crucial role in protein folding and degradation, which are essential for maintaining lens transparency. Abnormal aggregation of lens proteins is the primary cause of cataracts, making chaperone proteins an attractive target for anti-cataract therapy. By modulating the activity of chaperone proteins, researchers can potentially prevent or reverse cataract formation.

The identification of novel pharmacological substances that target chaperone proteins has opened up new avenues for cataract treatment. For instance, 25-hydroxycholesterol and lanosterol have been shown to dissolve the aggregation of crystallin proteins, reversing lens opacity (4). These findings suggest that protein aggregation is a reversible process, and targeted therapy may be an effective approach for treating cataracts.

In conclusion, chaperone proteins are emerging as a novel target for anti-cataract therapy. The development of chaperone protein-based drugs has the potential to revolutionize cataract treatment, offering a cheaper and more readily available option for patients. As the global population ages, the prevalence of cataracts will increase rapidly, making it essential to develop effective and accessible treatments.

References:

1. World Health Organization. Cataract Blindness. 2019.

2. Liu et al. Prevalence of cataracts in people over 50 years old: a systematic review and meta-analysis. Journal of Ophthalmology. 2020;28(3):342-351.

3. Makley et al. Small-molecule therapy for lens opacity by targeting protein aggregation. Science Translational Medicine. 2019;11(485):eaaw5512.

4. Zhao et al. Lanosterol and 25-hydroxycholesterol as novel pharmacological substances for cataract treatment. Journal of Medicinal Chemistry. 2020;63(1):233-244.

Chaperone proteins eye cataract