Regulation of lens water content: Effects on the physiological optics of the lens

Donaldson, Paul J.; Chen, Yadi; Petrova, Rosica S.; Grey, Angus C.; Lim, Julie C.

doi:10.1016/j.preteyeres.2022.101152

Cited by 16 publications

(22 citation statements)

References 176 publications

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“…LECs lesions are the main cause of cataracts [ 37 ]. Cataract occur due to a loss of transparency in the crystalline lens of the eye, which is the leading cause of blindness in the world [ 38 ]. Currently, surgery is the only effective solution, but cataract surgeries are a kind of burden for healthcare costs owing to the sheer prevalence of the disease among aging populations [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Lanosterol regulates abnormal amyloid accumulation in LECs through the mediation of cholesterol pathway metabolism

Su,

Sun,

Cao

et al. 2024

Biochemistry and Biophysics Reports

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Section: Discussionmentioning

confidence: 99%

Lanosterol regulates abnormal amyloid accumulation in LECs through the mediation of cholesterol pathway metabolism

Su,

Sun,

Cao

et al. 2024

Biochemistry and Biophysics Reports

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“…However, age alone does not fully explain the development of ARC. Physiologically, the human lens is composed of 63% water and 35% protein ( 33 , 34 ). Changes in water content and protein aggregation abnormalities in cataracts are the result of exposure to ultraviolet and x-ray radiation, steroids, and other chemicals and drugs, as well as the presence of local or systemic diseases such as diabetes, smoking, and malnutrition, rendering the normally transparent lens opaque ( 1 , 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, THs regulate the body’s water balance, and lens water transport is a critical physiological process for maintaining lens function and image quality. The effect of THs on systemic and local water balance is important in lens lesions ( 34 ). We hypothesize that one of the reasons hypothyroidism increases the risk of ARC is due to the disruption of water metabolism associated with thyroid hormone deficiency, and that water retention may have an effect on ocular tissues and the lens.…”

Section: Discussionmentioning

confidence: 99%

Hypothyroidism is a causal determinant of age-related cataract risk in European population: a Mendelian randomization study

Liu,

Sun,

et al. 2024

Front. Endocrinol.

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ObjectiveTo determine whether there is a causal relationship between thyroid dysfunction and the risk of age-related cataract (ARC) in the European population.DesignA two-sample Mendelian randomization (MR) study.MethodsHypothyroidism, hyperthyroidism, free thyroxine (fT4), and thyrotropin (TSH) were selected as exposures. The single nucleotide polymorphisms (SNP) of hypothyroidism and hyperthyroidism were obtained from the genome-wide association studies (GWAS) of the IEU database, including 337,159 subjects. Data for fT4 and TSH (72,167 subjects) were extracted from the ThyroidOmics Consortium. ARC was used as the outcome. The SNPs associated with ARC were selected from a GWAS of 216,362 individuals in the FinnGen database. The main method used was the inverse variance-weighted method, together with four complementary methods. Sensitivity analyses were performed using Cochran’s Q test, MR-PRESSO, MR-Egger regression and leave-one-out test. MR pleiotropy was used to test for pleiotropy. MR Steiger test was used to test for the directionality.ResultsTwo-sample MR analysis revealed a positive association between genetically predicted hypothyroidism and risk of ARC (OR = 2.501, 95% CI: 1.325-4.720; P = 0.004). Hyperthyroidism, circulating fT4 and TSH levels did not have a significant causal effect on ARC (P > 0.05). The results were robust and reliable, and no horizontal pleiotropy was found after sensitivity analyses. In the MR Steiger test, we found no reverse causal effects of hypothyroidism on the ARC (P <0.001).ConclusionsOur study provides strong evidence that hypothyroidism is a causal determinant of ARC risk.

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“…With regard to generating ‘squeezing’ forces within the lens, it is worth noting that the contractile proteins actin and myosin are present in the outer fibre cells, and that treatments which disrupt actin-myosin binding have measurable effects on the mechanical properties of the lens [ 44 ]. Others have argued that the water gradients associated with the GRIN are produced via an internal microcirculation system driven ultimately by sodium/potassium-ATPase activity in the outer cells [ 45 ]. No doubt additional mechanisms could be envisaged.…”

Section: Discussionmentioning

confidence: 99%

The effect of fibre cell remodelling on the power and optical quality of the lens

Rodriguez,

Tan,

Šikić

et al. 2023

J. R. Soc. Interface.

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Vertebrate eye lenses are uniquely adapted to form a refractive index gradient (GRIN) for improved acuity, and to grow slowly in size despite constant cell proliferation. The mechanisms behind these adaptations remain poorly understood. We hypothesize that cell compaction contributes to both. To test this notion, we examined the relationship between lens size and shape, refractive characteristics and the cross-sectional areas of constituent fibre cells in mice of different ages. We developed a block-face imaging method to visualize cellular cross sections and found that the cross-sectional areas of fibre cells rose and then decreased over time, with the most significant reduction occurring in denucleating cells in the adult lens cortex, followed by cells in the embryonic nucleus. These findings help reconcile differences between the predictions of lens growth models and empirical data. Biomechanical simulations suggested that compressive forces generated from continuous deposition of fibre cells could contribute to cellular compaction. However, optical measurements revealed that the GRIN did not mirror the pattern of cellular compaction, implying that compaction alone cannot account for GRIN formation and that additional mechanisms are likely to be involved.

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Regulation of lens water content: Effects on the physiological optics of the lens

Cited by 16 publications

References 176 publications

Lanosterol regulates abnormal amyloid accumulation in LECs through the mediation of cholesterol pathway metabolism

Lanosterol regulates abnormal amyloid accumulation in LECs through the mediation of cholesterol pathway metabolism

Hypothyroidism is a causal determinant of age-related cataract risk in European population: a Mendelian randomization study

The effect of fibre cell remodelling on the power and optical quality of the lens

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