Translational Vision Science & Technology Cover Image for Volume 14, Issue 4
April 2025
Volume 14, Issue 4
Open Access
Letters to the Editor  |   April 2025
The Future of Retinitis Pigmentosa Research: Unlocking the Potential of Branched-Chain Amino Acid Therapy
Author Affiliations
  • Qinling Jiang
    Southwest Medical University, Luzhou City, Sichuan Province, China
  • Lin Mou
    Department of Ophthalmology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou City, Sichuan Province, China. e-mail: [email protected]
Translational Vision Science & Technology April 2025, Vol.14, 10. doi:https://doi.org/10.1167/tvst.14.4.10
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      Qinling Jiang, Lin Mou; The Future of Retinitis Pigmentosa Research: Unlocking the Potential of Branched-Chain Amino Acid Therapy. Trans. Vis. Sci. Tech. 2025;14(4):10. https://doi.org/10.1167/tvst.14.4.10.

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We carefully reviewed the recent study by Hanako O. Ikeda et al., titled “Efficacy and Safety of Branched Chain Amino Acids on Retinitis Pigmentosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.”1 This study aimed to evaluate the efficacy and safety of oral branched-chain amino acids (BCAAs) in the progression of retinitis pigmentosa (RP) in patients. The results showed that although the BCAA combination granules (TK-98) did not demonstrate significant efficacy in patients with RP, their safety was confirmed. This finding lays the groundwork for future exploration of the potential role of BCAAs in treating this disease, which holds substantial clinical implications for both healthcare providers and patients. The data are reliable, the study design is rigorous, and it thoroughly considers the demographic and clinical characteristics of the subjects, offering new insights and valuable guidance for the clinical management of RP. However, to further refine the results and enhance their reliability, we propose the following constructive suggestions: 
RP encompasses a spectrum of inherited retinal degenerative diseases.2 The variability in clinical manifestations among patients with RP may influence the efficacy of BCAAs. The stratification factors used in this study are primarily based on age and mean deviation (MD) values; however, these may not fully capture the heterogeneity within the RP patient population. Future research should incorporate additional stratification factors, such as the patient’s genetic background (e.g. genotype, including genetic screening results), disease progression stage (e.g. early, intermediate, or late clinical stages), and quality of life measures (e.g. visual function-based scores) to minimize potential confounding factors and ensure balance across these critical variables. Alternatively, subgroup analyses based on patient characteristics, such as genotype (e.g. EYS gene mutation), disease stage, and gender, may provide insights into efficacy differences among specific subgroups. Second, as a nutritional supplement, the ability of BCAAs to penetrate the retina and exert their effects remains to be validated. Future studies should focus on pharmacokinetic and pharmacodynamic analyses of BCAAs, including assessments of bioavailability, plasma concentration, and the capacity to cross both the blood-brain barrier and the blood-retina barrier, to explore their pharmacokinetic profiles in the human body. Additionally, exploratory research into biomarkers, genomics, or metabolomics could be conducted to identify potential biomarkers (e.g. inflammatory factors and oxidative stress markers) for evaluating BCAAs’ efficacy in treating RP. Investigating whether BCAAs modulate the mTOR pathway (a key regulator of cell growth, metabolism, survival, and stress response) to enhance retinal cell repair or anti-inflammatory responses could provide insight into their potential mechanisms of action in RP, thereby optimizing treatment strategies.3 Third, in addition to utilizing ellipsoid zone length and fundus autofluorescence (FAF) images, supplementary indicators such as the thickness of the retinal nerve fiber layer (RNFL), changes in macular region thickness, the cup-to-disc ratio of the optic disc, and the health status of retinal vessels can be employed to assess morphological changes in the retina. This comprehensive approach provides more robust data on retinal function and structural alterations, offering a better reflection of ocular pathological changes.4 Furthermore, morphological changes in the fundus and the fine retinal structures typically require substantial time to become apparent. Future studies should consider using imaging techniques, such as optical coherence tomography (OCT), fundus photography, and scanning OCT, to establish a morphology scoring system that tracks dynamic changes by regularly comparing retinal morphology at different time points. This would enable a more precise assessment of the protective effects of drugs on retinal structures. Last, considering that RP may involve neurodegenerative changes, future research could incorporate cognitive function tests to evaluate the dual impact of drugs on both retinal and brain functions.5 Monitoring the functionality of the visual cortex may uncover new insights into the treatment of RP. 
This study offers valuable insights and considerations for the clinical treatment of RP. We would like to express our sincere gratitude to the healthcare institutions, public health professionals, social workers, and government officials for their collaboration and commitment, which made this research possible. The findings are of considerable regional significance and provide a foundation for further investigations into related areas in other countries. Future research should build on this foundation to devise more effective strategies and enhance our exploration and understanding of disease treatment options for RP. 
References
Ohashi Ikeda H, Hasegawa T, Abe H, et al. Efficacy and safety of branched chain amino acids on retinitis pigmentosa: a randomized, double-blind, placebo-controlled clinical trial. Transl Vis Sci Technol. 2024; 13(8): 29. [CrossRef]
Dias MF, Joo K, Kemp JA, et al. Molecular genetics and emerging therapies for retinitis pigmentosa: basic research and clinical perspectives. Prog Retin Eye Res. 2018; 63: 107–131. [CrossRef] [PubMed]
Gong Q, Wang J, Luo D, et al. Accumulation of branched-chain amino acids deteriorates the neuroinflammatory response of Müller cells in diabetic retinopathy via leucine/Sestrin2-mediated sensing of mTOR signaling. Acta Diabetol. 2024; 62(2): 227–240. [CrossRef] [PubMed]
Sadda SR, Guymer RH, Holz FG, et al. Consensus definition for atrophy associated with age-related macular degeneration on OCT. Ophthalmology. 2018; 125(4): 537–548. [CrossRef] [PubMed]
London A, Benhar I, Schwartz M. The retina as a window to the brain—from eye research to CNS disorders. Nat Rev Neurol. 2012; 9(1): 44–53. [CrossRef] [PubMed]
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