The Physiology of Lens Transparency: New Insights into Presbyopia and Cataract

Purpose. Studies involving genotyping of STR markers at 2q34 have repeatedly found the region to host the disease haplotype for pediatric cataract. Present study investigated the association of D2S2944 marker, in sperm associated antigen 16 (SPAG16) gene and rs2289917 polymorphism, in γ-crystallin B gene, with childhood cataract. Methods. 97 pediatric cataract cases and 110 children with no ocular defects were examined for tetranucleotide repeat marker/SNP using PCR-SSLP/RFLP techniques. Polymorphisms were assessed for association using contingency tables and linkage disequilibrium among alleles of the markers was estimated. Energy-optimization program predicted the secondary structure models of repeats of D2S2944. Results. Seven alleles of D2S2944, with 9–15 “GATA” repeats, were observed. Frequency of the longer allele of D2S2944, ≥(GATA)13 repeats, was 0.73 in cases and 0.56 in controls (P=0.0123). Male children bearing ≥(GATA)13 repeats showed >3-fold higher risk for cataract (CI95% = 1.43–7.00, P=0.0043, Pc=0.0086) as compared to female children (OR=1.19, CI95% = 0.49–2.92, P=0.70). Cases with haplotype—≥(GATA)13 of D2S2944 and “C” allele rs2289917—have a higher risk for pediatric cataract (OR=2.952, CI95% = 1.595~5.463, P=0.000453). >(GATA)13 repeats formed energetically more favorable stem-loop structure. Conclusion. Intragenic microsatellite repeat expansion in SPAG16 gene increases predisposition to pediatric cataract by probably interfering posttranscriptional events and affecting the expression of adjacent lens transparency gene/s in a gender bias manner.

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Biological glass: structural determinants of eye lens transparency

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2010.0302 ◽

2011 ◽

Vol 366 (1568) ◽

pp. 1250-1264 ◽

Cited By ~ 148

Author(s):

Steven Bassnett ◽

Yanrong Shi ◽

Gijs F. J. M. Vrensen

Keyword(s):

Refractive Index ◽

Cellular Level ◽

Structural Determinants ◽

Lens Transparency ◽

Index Matching ◽

Lens Fibre ◽

Refractive Index Matching ◽

Lens Membranes ◽

Adhesive Proteins ◽

Structural Adaptations

The purpose of the lens is to project a sharply focused, undistorted image of the visual surround onto the neural retina. The first pre-requisite, therefore, is that the tissue should be transparent. Despite the presence of remarkably high levels of protein, the lens cytosol remains transparent as a result of short-range-order interactions between the proteins. At a cellular level, the programmed elimination of nuclei and other light-scattering organelles from cells located within the pupillary space contributes directly to tissue transparency. Scattering at the cell borders is minimized by the close apposition of lens fibre cells facilitated by a plethora of adhesive proteins, some expressed only in the lens. Similarly, refractive index matching between lens membranes and cytosol is believed to minimize scatter. Refractive index matching between the cytoplasm of adjacent cells is achieved through the formation of cellular fusions that allow the intermingling of proteins. Together, these structural adaptations serve to minimize light scatter and enable this living, cellular structure to function as ‘biological glass’.

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Ultraviolet-sensitive vision in long-lived birds

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2010.1100 ◽

2010 ◽

Vol 278 (1702) ◽

pp. 107-114 ◽

Cited By ~ 24

Author(s):

Livia S. Carvalho ◽

Ben Knott ◽

Mathew L. Berg ◽

Andrew T. D. Bennett ◽

David M. Hunt

Keyword(s):

Uv Light ◽

Bird Species ◽

Visual Sensitivity ◽

Opsin Gene ◽

Uv Sensitivity ◽

Long Period ◽

Lens Transparency ◽

Avian Order

Long-term exposure to ultraviolet (UV) light generates substantial damage, and in mammals, visual sensitivity to UV is restricted to short-lived diurnal rodents and certain marsupials. In humans, the cornea and lens absorb all UV-A and most of the terrestrial UV-B radiation, preventing the reactive and damaging shorter wavelengths from reaching the retina. This is not the case in certain species of long-lived diurnal birds, which possess UV-sensitive (UVS) visual pigments, maximally sensitive below 400 nm. The Order Psittaciformes contains some of the longest lived bird species, and the two species examined so far have been shown to possess UVS pigments. The objective of this study was to investigate the prevalence of UVS pigments across long-lived parrots, macaws and cockatoos, and therefore assess whether they need to cope with the accumulated effects of exposure to UV-A and UV-B over a long period of time. Sequences from the SWS1 opsin gene revealed that all 14 species investigated possess a key substitution that has been shown to determine a UVS pigment. Furthermore, in vitro regeneration data, and lens transparency, corroborate the molecular findings of UV sensitivity. Our findings thus support the claim that the Psittaciformes are the only avian Order in which UVS pigments are ubiquitous, and indicate that these long-lived birds have UV sensitivity, despite the risks of photodamage.

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Cataract-causing G91del mutant destabilised βA3 heteromers formation linking with structural stability and cellular viability

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-320033 ◽

2021 ◽

pp. bjophthalmol-2021-320033

Author(s):

Huaxia Wang ◽

Qing Tian ◽

Jingjie Xu ◽

Wanyue Xu ◽

Ke Yao ◽

...

Keyword(s):

Structural Stability ◽

Cell Apoptosis ◽

Guanidine Hydrochloride ◽

Pathogenic Mutation ◽

Dynamics Simulation ◽

Size Exclusion ◽

Cellular Viability ◽

Structural Protein ◽

Lens Transparency ◽

Exclusion Chromatography

Background/aimsCongenital cataracts, which are genetically heterogeneous eye disorders, result in visual loss in childhood around the world. CRYBA1/BA3 serves as an abundant structural protein in the lens, and forms homomers and heteromers to maintain lens transparency. In previous study, we identified a common cataract-causing mutation, βA3-glycine at codon 91 (G91del) (c.271–273delGAG), which deleted a highly conserved G91del and led to perinuclear zonular cataract. In this study, we aimed to explore the underlying pathogenic mechanism of G91del mutation.MethodsProtein purification, size-exclusion chromatography, spectroscopy and molecular dynamics simulation assays were used to investigate the effects on the heteromers formation and the protein structural properties of βA3-crystallin caused by G91del mutation. Intracellular βA3-G91del overexpression, MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide) and cell apoptosis were used to investigate the cellular functions of βA3-G91del.ResultsβA3-crystallin and βB2-crystallin could form heteromers, which have much more stable structures than βA3 homomers. Interestingly, βA3/βB2 heteromers improved their resistance against the thermal stress and the guanidine hydrochloride treatment. However, the pathogenic mutation βA3-G91del destroyed the interaction with βB2, and thereby decreased its structural stability as well as the resistance of thermal or chemical stress. What’s more, the βA3-G91del mutation induced cell apoptosis and escaped from the protection of βB2-crystallin.ConclusionsβA3/βB2 heteromers play an indispensable role in maintaining lens transparency, while the βA3-G91del mutation destabilises heteromers formation with βB2-crystallin, impairs cellular viability and induces cellular apoptosis. These all might contribute to cataract development.

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