Basic Science of the Lens

Dai, Eric; Boulton, Michael E.

doi:10.1016/b978-0-323-04332-8.00057-3

Cited by 5 publications

(9 citation statements)

References 41 publications

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“…Within the lens, the epithelium lies anteriorly and, paralleling the cornea, has less proliferative capacity centrally. 30 This anterior lens epithelium expresses miR-184, 9 adjacent to the site of the cataract in the affected family.…”

mentioning

confidence: 99%

Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract

Hughes

Bradley

Campbell

et al. 2011

The American Journal of Human Genetics

240

229

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MicroRNAs (miRNAs) bind to complementary sequences within the 3' untranslated region (UTR) of mRNAs from hundreds of target genes, leading either to mRNA degradation or suppression of translation. We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract by deep sequencing of a linkage region known to contain the mutation. The mutant form fails to compete with miR-205 (MIR205) for overlapping target sites on the 3' UTRs of INPPL1 and ITGB4. Although these target genes and miR-205 are expressed widely, the phenotype is restricted to the cornea and lens because of the very high expression of miR-184 in these tissues. Our finding highlights the tissue specificity of a gene network regulated by a miRNA. Awareness of the important function of miRNAs could aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.

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mentioning

confidence: 99%

Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract

Hughes

Bradley

Campbell

et al. 2011

The American Journal of Human Genetics

240

229

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“…The lateral membranes of epithelial cells (membranes in contact with the adjacent epithelial cells) are highly tortuous (Dai & Boulton ). We show in detail their appearance on the LECs forming the confluent monolayer by SEM.…”

Section: Discussionmentioning

confidence: 99%

Morphological and proliferative studies on ex vivo cultured human anterior lens epithelial cells – relevance to capsular opacification

Andjelić

Drašlar

Lumi

et al. 2015

Acta Ophthalmologica

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ABSTRACT.Purpose: To determine the structural characteristics of lens epithelial cells (LECs) found on the anterior portion of the lens capsule and their pluripotency, proliferating and migrating potential when grown ex vivo with relevance to posterior capsular opacification (PCO) after cataract surgery. Methods: The explants of anterior portion of the lens capsule consisting of monolayer of LECs were obtained from uneventful cataract surgery and were cultivated under adherent conditions. The size and shape of the outgrowing cells were recorded by scanning electron microscopy (SEM), while their migration and proliferation potential were followed using light microscopy. Positivity for proliferation (Ki-67)-and pluripotency (Sox2)-specific markers were tested by immunofluorescent staining. Results: The proliferation and migration of anterior portion of the lens capsule's LECs filling up the denuded and reverse side regions of the lens capsule as well as their growth on glass culture surfaces could be followed by light microscopy and SEM, while the distribution of LECs and their morphology could be analysed in detail by SEM. The expression of Ki-67 and Sox2 in LECs growing adherently on human anterior portion of the lens capsule could also be detected. Conclusions: Classic light microscopy and SEM can be used to show that human anterior portion of the lens capsule harbours LECs that can proliferate and migrate, suggesting their pluripotency or putative stem cell nature. Similarly, morphological techniques can be used to study PCO and the effect different drugs or physical treatments have against PCO development.

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“…The main function of the lens is to change the focal distance of the eye, which ensures the formation of a clear image to the retina with various object distances. The lens consists of the lens capsule, lens anterior epithelial cell monolayer, and lens fiber cells (Figure S1). The lens capsule surrounds the epithelial and fiber cells of the lens and allows the permeation of even large molecules to the lens. − The lens epithelial cell layer lies in the anterior lens and possesses tight junctions .…”

Section: Introductionmentioning

confidence: 99%

“…The lens fiber cells can be further divided into loosely structured lens cortex, which consists of the young lens fiber cells, and dense lens nucleus, which consists of the oldest. The main components of the lens are water and proteins, mainly various crystallins, and their concentrations vary between the lens cortex and nucleus, the cortex having higher water and lower protein content than the nucleus . The lens lipids contain a high level of cholesterol, and they are mostly associated with proteins in the cell membranes .…”

Section: Introductionmentioning

confidence: 99%

“…The main components of the lens are water and proteins, mainly various crystallins, and their concentrations vary between the lens cortex and nucleus, the cortex having higher water and lower protein content than the nucleus. 1 The lens lipids contain a high level of cholesterol, and they are mostly associated with proteins in the cell membranes. 6 Thus, the lipid content of lens also increases from the cortex to the nucleus.…”

Section: Introductionmentioning

confidence: 99%

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Distribution of Small Molecular Weight Drugs into the Porcine Lens: Studies on Imaging Mass Spectrometry, Partition Coefficients, and Implications in Ocular Pharmacokinetics

et al. 2019

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Lens is the avascular tissue in the eye between the aqueous humor and vitreous. Drug binding to the lens might affect ocular pharmacokinetics, and the binding may also have a pharmacological role in drug-induced cataract and cataract treatment. Drug distribution in the lens has been studied in vitro with many compounds; however, the experimental methods vary, no detailed information on distribution between the lens sublayers exist, and the partition coefficients are reported rarely. Therefore, our objectives were to clarify drug localization in the lens layers and establish partition coefficients for a wide range of molecules. Furthermore, we aimed to illustrate the effect of lenticular drug binding on overall ocular drug pharmacokinetics. We studied the distribution of 16 drugs and three fluorescent dyes in whole porcine lenses in vitro with imaging mass spectrometry and fluorescence microscopy techniques. Furthermore, we determined lens/buffer partition coefficients with the same experimental setup for 28 drugs with mass spectrometry. Finally, the effect of lenticular binding of drugs on aqueous humor drug exposure was explored with pharmacokinetic simulations. After 4 h, the drugs and the dyes distributed only to the outermost lens layers (capsule and cortex). The lens/buffer partition coefficients for the drugs were low, ranging from 0.05 to 0.8. On the basis of the pharmacokinetic simulations, a high lens-aqueous humor partition coefficient increases drug exposure in the lens but does not significantly alter the pharmacokinetics in the aqueous humor. To conclude, the lens seems to act mainly as a physical barrier for drug distribution in the eye, and drug binding to the lens affects mainly the drug pharmacokinetics in the lens.

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Basic Science of the Lens

Cited by 5 publications

References 41 publications

Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract

Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract

Morphological and proliferative studies on ex vivo cultured human anterior lens epithelial cells – relevance to capsular opacification

Distribution of Small Molecular Weight Drugs into the Porcine Lens: Studies on Imaging Mass Spectrometry, Partition Coefficients, and Implications in Ocular Pharmacokinetics

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