Hallmarks of lens aging and cataractogenesis

Wishart, Tayler F.L.; Flokis, Mary; Shu, Daisy Y.; Das, Shannon; Lovicu, Frank J.

doi:10.1016/j.exer.2021.108709

Cited by 30 publications

(22 citation statements)

References 321 publications

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“…With aging, LECs undergo numerous biochemical and biophysical changes, which induces structural and functional impairment, leading to EMT development and autophagy activation[ 47 ]. Previous studies have indicated that mTORC1 possibly promotes the development of cataract through controlling cellular EMT and inhibiting the level of autophagy through related signaling proteins.…”

Section: Discussionmentioning

confidence: 99%

Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study

Cai

Liu

et al. 2022

BMC Genomics

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Background The mechanistic target of rapamycin (mTOR) signal pathway plays a critical regulating role in the occurrence and development of cataract. However, the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic initiation factor 4A (EIF-4A), in regulating cataract development is still unknown. Herein, we conducted a mendelian randomization (MR) study to understand the function of mTORC1 signaling in the process of cataract development. Results The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. RAPS). The single-nucleotide polymorphisms (SNPs), P<5 × 10− 6 and r2<0.05, were selected to genetically predict the RP-S6K, EIF4EBP, EIF-4E, EIF-4A, and EIF-4G. We included a total of 26,758 cases and 189,604 controls in this MR study. The study revealed causal association between circulating EIF4EBP (OR 1.09, 95% confidence interval 1.03,1.16, P = 0.004), RP-S6K (OR 1.04, 95% confidence interval 1.01, 1.08, P = 0.02) and cataract formation with IVW estimate. Whereas after correcting outliers, MR robust adjusted profile score (MR. RAPS) shows consistent result with IVW for EIF4EBP (OR = 1.08, 95%CI:1.05–1.11, P = 0.007). The observation strengthened the confidence in the true causal associations. However, no association was found for circulating EIF-4E (OR 1.03, 95% confidence interval 0.97, 1.09, P = 0.31), EIF-4A (OR 1.02, 95% confidence interval 0.98, 1.07, P = 0.34), and EIF-4G (OR 1.02, 95% confidence interval 0.94, 1.01, P = 0.64) levels with cataract formation. No evidence of heterogeneity and unbalanced horizontal pleiotropy was detected. Conclusion The MR study suggests that EIF4EBP is a high-risk factor for cataract development. There may be a potential causal association between the mTORC1/EIF4EBP axis and cataract. This research highlights the potential mechanism for cataract development and a genetic target to prevent as well as treat cataracts.

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Section: Discussionmentioning

confidence: 99%

Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study

Cai

Liu

et al. 2022

BMC Genomics

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“…An alternative to Matrigel is to prepare proteins from bovine lens capsules at a large scale or to model capsule protein composition using ECM proteins collagen IV, laminin, and smaller amounts of nidogen and perlecan [ 250 , 251 ]. Additional proteins to include are various heparane sulfate proteoglycans as they bind FGF1 and FGF2 [ 252 , 253 ] as well as entactin [ 254 ].…”

Section: 3d-eye Organoids: Experimental Challenges and In Vitro Model...mentioning

confidence: 99%

Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology

Cvekl

Camerino

2022

Cells

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In vitro differentiation of human pluripotent stem cells (hPSCs) into specialized tissues and organs represents a powerful approach to gain insight into those cellular and molecular mechanisms regulating human development. Although normal embryonic eye development is a complex process, generation of ocular organoids and specific ocular tissues from pluripotent stem cells has provided invaluable insights into the formation of lineage-committed progenitor cell populations, signal transduction pathways, and self-organization principles. This review provides a comprehensive summary of recent advances in generation of adenohypophyseal, olfactory, and lens placodes, lens progenitor cells and three-dimensional (3D) primitive lenses, “lentoid bodies”, and “micro-lenses”. These cells are produced alone or “community-grown” with other ocular tissues. Lentoid bodies/micro-lenses generated from human patients carrying mutations in crystallin genes demonstrate proof-of-principle that these cells are suitable for mechanistic studies of cataractogenesis. Taken together, current and emerging advanced in vitro differentiation methods pave the road to understand molecular mechanisms of cataract formation caused by the entire spectrum of mutations in DNA-binding regulatory genes, such as PAX6, SOX2, FOXE3, MAF, PITX3, and HSF4, individual crystallins, and other genes such as BFSP1, BFSP2, EPHA2, GJA3, GJA8, LIM2, MIP, and TDRD7 represented in human cataract patients.

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“…However other mechanisms intricate are needed to be explored; a pyroptosis is a form of lytic programmed cell death, highly associated with inflammation due to the rupture of proinflammatory cells content, not only in cataracts formation, perhaps pathogen infections, bacteria's, apoptosis are linked to REDOX. The participation of the expression of caspase-1 and interleukin (IL-1B) in the anterior capsule cataract formation, increased in the LEC induced previously with hydrogen peroxide, relevant because they are today´s material to delimit caspase 1 as the first caspase cell in mammals to be identified to be enrolled with apoptosis, mediating pro-inflammatory pyroptosis, secondary to external or internal aggressions [32][33][34][35][36][37][38][39][40][41][42][43].…”

Section: Molecular Biology In Lens Opacitymentioning

confidence: 99%

Reactive Oxygen Species and Eye Aging in Cataracts through Biomolecular Mechanisms

Pacheco

2022

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The cataractogenesis process and the novel mechanisms involved in its progression make us question that the only solution today presented for its resolution is through a surgical procedure. The unveiling of such interesting and intricate machinery in the lens opacification occupies not only the ophthalmologists field, but also biology, molecular, and biochemistry areas. The animal models, experimental and theoretically, have done their best try to present what appears to be an irreparable and unstoppable process nowadays. The crystalline lens opacification is chronic and progressively damaged due to the loss of balance between the production and elimination of free reactive oxygen species (ROS), the attempts to stop or slow down this overproduction or lack of elimination lie in study material from disciplines as complex as cancer pathways. The execution of this review article was possible through metasearch engines like Wiley Online Library, EBSCO, Cochrane, Clinical key and MEDLINE PubMed (National Library of Medicine, National Institutes of Health), to retrieve studies from January 2021 to January 2022, following PRISMA guidelines, with a special affinity to systematic reviews and meta-analysis. MeSH Terms associated with "Cataract AND Reactive Oxygen Species". This work constitutes an integral cataractogenesis view in the development of future therapeutic scopes. The world population especially in Europe is aging at a rapid rate, in this sense is necessary to consider a root potential solution and not palliative strategies in ophthalmology for the next generations. The compendium of procedures presented already supposed to open a new panorama to a clearer world, a world without senile cataracts. Time is vision.

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Hallmarks of lens aging and cataractogenesis

Cited by 30 publications

References 321 publications

Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study

Association of mTORC1‑dependent circulating protein levels with cataract formation: a mendelian randomization study

Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology

Reactive Oxygen Species and Eye Aging in Cataracts through Biomolecular Mechanisms

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