Oxidative Stress and Cataract Formation: Evaluating the Efficacy of Antioxidant Therapies
Abstract
:1. Introduction
2. The Structure and Physiology of the Lens
Physiology of the Lens and Its Redox Regulatory Mechanisms
3. Ocular Damages Induced by Reactive Oxygen Species: Cataracto-genesis
3.1. Antioxidative Systems
3.2. Protein Aggregation, Cross-Linking, and Light-Scattering
3.3. Lipid Peroxidation and Loss of Membrane Integrity
4. Antioxidant Strategies for the Prevention and Management of Cataracts
4.1. Dietary Nutrients and Supplements
4.1.1. Vitamins C and E
4.1.2. Lutein and Zeaxanthin
4.2. Potential Pharmacological Agents with Antioxidative Properties for Cataract Prevention and Treatment
4.2.1. N-acetyl-carnosine
4.2.2. N-acetylcysteine Amide
4.2.3. Resveratrol
4.2.4. Baicalein
4.2.5. Metformin
4.3. Nanotechnology-Based Drug Delivery Systems for Cataract Prevention and Treatment
4.3.1. N-acetylcarnosine Nanoparticles
4.3.2. Resveratrol Nanoparticles and Nanovesicles
4.3.3. Baicalin
4.3.4. Cerium Oxide
4.4. Gene Therapy for Cataract Prevention and Treatment
4.4.1. Suicide Gene Therapy
4.4.2. RNA Interference
4.4.3. CRISPR-Cas9
5. Challenges and Limitations of Antioxidants and Novel Therapeutic Approaches
6. Recommendations and Future Directions
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Treatment | Structure and Description | Implications for Cataract Treatment | References |
---|---|---|---|
N-acetylcarnosine | Prodrug of l-carnosine. | Reduces lens opacification in canine cataracts, NACS eyedrops improve visual acuity and glare sensitivity in humans with cataracts. | [107,108,109] |
N-acetylcysteine amide | Analog of NAC, a glutathione prodrug. | NACA intraperitoneal injection prevents sodium selenite-induced cataract formation in rats, NACA eye drops reverse sodium selenite-induced cataract grade in rats, NACA and diNACA reduce H2O2-induced lens opacity in pig and rat lenses, with NACA increasing antioxidant levels as well. | [110,111] |
diNACA | Analog of NACA. | ||
Resveratrol | Polyphenolic phytoalexin produced in plants, trans isomer is more bioactive. | Delays diabetic cataract formation in rats, mitigates oxygen-mediated protein oxidation in diabetic rats, protects human lens epithelial cells against oxidative damage, increases antioxidant levels and delays lenticular opacity in rats with naphthalene-induced cataracts. | [112,113,114,115] |
Baicalein | Antioxidant flavonoid. | In rats with sodium-selenite induced cataracts, it decreases dense opacity of the lens, increases soluble protein content, reduces oxidative stress, and prevents damage of lens epithelial cells. | [116] |
Metformin | Chronic low dose of metformin in mice significantly decreased lens opacity and lens epithelial cell senescence, which increasing autophagy. | [117] |
Drug | Nanotechnology Used | Outcomes | Reference |
---|---|---|---|
NACS | Encapsulated NACS into gold nanoparticles. | Attenuated NACS toxicity at high concentrations, increased biocompatibility and bioavailability. | [123] |
Resveratrol | Encapsulated resveratrol into lipid cyclodextrin-based nanoparticles. | Increased levels of antioxidant markers in bovine lens cultures to a higher degree than resveratrol alone. | [124] |
Resveratrol | Encapsulated resveratrol into niosomes. | Maintained antioxidant capacity of resveratrol, prevented light irradiation-induced isomer conversion of resveratrol to its less bioactive cis isomer. | [115] |
Baicalin | Encapsulated baicalin into chitosan-coated mPEG-PLGA nanoparticles. | Increased cellular uptake of baicalin, increased corneal retention of baicalin in rabbits, increased antioxidant levels and decreased oxidative stress markers in rabbits with selenite-induced cataract to a greater degree than baicalin alone. | [125] |
CeO2 | Encapsulated CeO2 in PEG-PLGA coated nanoparticles. | Allowed for water soluble formation of CeO2 suitable for biological use. Decreased peroxide and superoxide concentrations in lens epithelial cell cultures. Reduced oxidative stress markers, increased antioxidant levels, and attenuated cataract development in rats with diabetic cataracts. | [126] |
Gene(s) of Interest | Outcomes | Reference |
---|---|---|
Suicide Gene Therapy | ||
Procaspase 3 or Bax | Overexpression of pro-apoptotic molecules was successfully targeted to rabbit residual lens epithelial cells, and sufficiently prevented PCO in rabbits. | [133,134] |
HSV-tk (plus treatment with GNV) | HSV-tk was successfully expressed in HLECs and, when treated with GNV, was able to cause cell death. | [135] |
RNA Interference | ||
EGF | siRNA successfully inhibited cell proliferation of HLECs and significantly reduced PCO in a rat model. | [136] |
EDIL3 | Knockdown significantly reduced HLEC proliferation and migration in vitro. | [137] |
TGF-βRII | RNAi significantly reduced LEC migration. | [138] |
Snail | siRNA successfully inhibited TGF-βII-mediated EMT of human epithelial cells. | [139] |
ILK | shRNA significantly decreased migration, increased apoptosis, and caused arresting of cells at G1/S transition. | [138] |
CRISPR-Cas9 | ||
TGF-βRII | TGF-βRII knockout caused significant decrease in PCO incidence for rabbit PCO model, as well as significant decreased in in vitro HLEC proliferation. | [130] |
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Kulbay, M.; Wu, K.Y.; Nirwal, G.K.; Bélanger, P.; Tran, S.D. Oxidative Stress and Cataract Formation: Evaluating the Efficacy of Antioxidant Therapies. Biomolecules 2024, 14, 1055. https://doi.org/10.3390/biom14091055
Kulbay M, Wu KY, Nirwal GK, Bélanger P, Tran SD. Oxidative Stress and Cataract Formation: Evaluating the Efficacy of Antioxidant Therapies. Biomolecules. 2024; 14(9):1055. https://doi.org/10.3390/biom14091055
Chicago/Turabian StyleKulbay, Merve, Kevin Y. Wu, Gurleen K. Nirwal, Paul Bélanger, and Simon D. Tran. 2024. "Oxidative Stress and Cataract Formation: Evaluating the Efficacy of Antioxidant Therapies" Biomolecules 14, no. 9: 1055. https://doi.org/10.3390/biom14091055