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Experimental Eye Research Mar 2017The crystalline lens plays an important role in the refractive vision of vertebrates by facilitating variable fine focusing of light onto the retina. Loss of lens... (Review)
Review
The crystalline lens plays an important role in the refractive vision of vertebrates by facilitating variable fine focusing of light onto the retina. Loss of lens transparency, or cataract, is a frequently acquired cause of visual impairment in adults and may also present during childhood. Genetic studies have identified mutations in over 30 causative genes for congenital or other early-onset forms of cataract as well as several gene variants associated with age-related cataract. However, the pathogenic mechanisms resulting from genetic determinants of cataract are only just beginning to be understood. Here, we briefly summarize current concepts pointing to differences in the molecular mechanisms underlying congenital and age-related forms of cataract.
Topics: Aging; Animals; Cataract; Crystallins; Humans; Lens, Crystalline; Mutation
PubMed: 27334249
DOI: 10.1016/j.exer.2016.06.011 -
International Immunology Nov 2017Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high... (Review)
Review
Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation. Additionally, hyperferritinemia is a key acute-phase reactants, used by clinicians as an indication for therapeutic intervention, aimed at controlling inflammation in high-risk patients. One school of thought maintains that hyperferritinemia is an 'innocent bystander' biomarker of uncontrolled inflammation that can be used to gauge effectiveness of intervention. Other schools of thought maintain that ferritin induction could be a protective negative regulatory loop. Others maintain that ferritin is a key mediator of immune dysregulation, especially in extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects. There is a clear need for further investigation of the role of ferritin in uncontrolled inflammatory conditions both as a biomarker and mediator of disease because its occurrence identifies patients with high mortality risk and its resolution predicts their improved survival.
Topics: Acute-Phase Reaction; Animals; Cataract; Ferritins; Hemochromatosis; Humans; Immunity, Innate; Immunomodulation; Inflammation; Iron; Iron Metabolism Disorders
PubMed: 28541437
DOI: 10.1093/intimm/dxx031 -
Annual Review of Vision Science Sep 2019Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or... (Review)
Review
Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or disruption of the lens microarchitecture. In general, genes involved in inherited cataracts reflect important processes and pathways in the lens including lens crystallins, connexins, growth factors, membrane proteins, intermediate filament proteins, and chaperones. Usually, mutations causing severe damage to proteins cause congenital cataracts, while milder variants increasing susceptibility to environmental insults are associated with age-related cataracts. These may have different pathogenic mechanisms: Congenital cataracts induce the unfolded protein response and apoptosis. By contrast, denatured crystallins in age-related cataracts are bound by α-crystallin and form light-scattering HMW aggregates. New therapeutic approaches to age-related cataracts use chemical chaperones to solubilize HMW aggregates, while attempts are being made to regenerate lenses using endogenous stem cells to treat congenital cataracts.
Topics: Apoptosis; Cataract; Crystallins; Eye Diseases, Hereditary; Humans; Stem Cell Transplantation
PubMed: 31525139
DOI: 10.1146/annurev-vision-091517-034346 -
Nature Mar 2016The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has...
The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.
Topics: Animals; Cataract; Cataract Extraction; Epithelial Cells; Eye Proteins; Homeodomain Proteins; Homeostasis; Humans; Lens, Crystalline; Macaca; PAX6 Transcription Factor; Paired Box Transcription Factors; Polycomb Repressive Complex 1; Proto-Oncogene Proteins; Recovery of Function; Regeneration; Repressor Proteins; Stem Cells; Vision, Ocular
PubMed: 26958831
DOI: 10.1038/nature17181 -
BMC Cell Biology Jan 2017The lens is an avascular organ composed of an anterior epithelial cell layer and fiber cells that form the bulk of the organ. The lens expresses connexin43 (Cx43),... (Review)
Review
The lens is an avascular organ composed of an anterior epithelial cell layer and fiber cells that form the bulk of the organ. The lens expresses connexin43 (Cx43), connexin46 (Cx46) and connexin50 (Cx50). Epithelial Cx50 has critical roles in cell proliferation and differentiation, likely involving growth factor-dependent signaling pathways. Both Cx46 and Cx50 are crucial for lens transparency; mutations in their genes have been linked to congenital and age-related cataracts. Congenital cataract-associated connexin mutants can affect protein trafficking, stability and/or function, and the functional effects may differ between gap junction channels and hemichannels. Dominantly inherited cataracts may result from effects of the connexin mutant on its wild type isotype, the other co-expressed wild type connexin and/or its interaction with other cellular components.
Topics: Animals; Cataract; Connexins; Humans; Intercellular Signaling Peptides and Proteins; Lens, Crystalline; Mutation; Signal Transduction
PubMed: 28124626
DOI: 10.1186/s12860-016-0116-6 -
Turkish Journal of Ophthalmology Apr 2021Congenital cataract is a challenging ophthalmological disorder which can cause severe visual loss. It can be diagnosed at birth or during the first year of life. Early... (Review)
Review
Congenital cataract is a challenging ophthalmological disorder which can cause severe visual loss. It can be diagnosed at birth or during the first year of life. Early diagnosis and treatment are crucial for the visual prognosis. It can be associated with various ocular and systemic abnormalities. Determining whether congenital cataract is isolated or associated with other pathology is an indispensable step for the prediction of potential vision as well as early diagnosis and treatment of conditions that can cause morbidity or mortality. Many genes have been identified in the molecular etiology of congenital cataract. Most mutations have been reported in the crystallin genes. Determination of the genetic cause may not only enable individualized genetic counseling but also help to identify concomitant ocular and/or systemic disorders depending on the characteristics of the genetic test used. Recently, next-generation sequencing in particular has become an evolving technology for determining the molecular etiology of congenital cataract and furthering our knowledge of the disease.
Topics: Cataract; Crystallins; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Mutation; Pedigree
PubMed: 33951899
DOI: 10.4274/tjo.galenos.2020.08377 -
Journal of Veterinary Diagnostic... Jan 2022A muskox neonate () that died of starvation was diagnosed with congenital lenticular anomalies that included spherophakia and hypermature cataract associated with...
A muskox neonate () that died of starvation was diagnosed with congenital lenticular anomalies that included spherophakia and hypermature cataract associated with probable lens-induced lymphocytic uveitis and neutrophilic keratitis. Impaired sight as a result of cataract and associated inflammation likely contributed to abandonment and starvation, although maternal death cannot be excluded definitively. Ocular lesions, such as congenital cataracts and spherophakia in neonates, may be important factors affecting survival in free-ranging animals.
Topics: Animals; Canada; Cataract; Northwest Territories; Ruminants; Starvation
PubMed: 34763579
DOI: 10.1177/10406387211057470 -
Romanian Journal of Morphology and... 2020Congenital cataract is one of the main causes of blindness in newborns and children. According to the World Health Organization (WHO), there are about 14 million...
Congenital cataract is one of the main causes of blindness in newborns and children. According to the World Health Organization (WHO), there are about 14 million children suffering from congenital cataract. Our study is based on 82 children, males - 46 (56.1%) and females - 36 (43.9%), with congenital cataract operated in the same ophthalmological centre in Bucharest, Romania. Of the 82 patients, 49 (59.76%) had bilateral cataract and 33 (40.24%) unilateral cataract. Clinically, the most frequent was the total cataract, followed by lamellar, nuclear and cerulean. We employed nine surgical approaches in our patients, depending on the type of intraocular lens (IOL). Morphologically, obvious changes were rendered evident at the level of anterior and posterior capsules, as well as subcapsular.
Topics: Cataract; Female; Humans; Male; Retrospective Studies
PubMed: 32747900
DOI: 10.47162/RJME.61.1.11 -
Indian Journal of Ophthalmology Dec 2022To study and describe clinical characteristics of congenital and developmental cataract at a tertiary eye care facility.
PURPOSE
To study and describe clinical characteristics of congenital and developmental cataract at a tertiary eye care facility.
METHODS
In this retrospective study, 942 children (1311 eyes) presenting with congenital/developmental cataract over a 10-year study period were included. Gender, age at surgery, main presenting complaint, morphologic type of cataract, laterality, family history, and associated findings were recorded.
RESULTS
The overall proportion of boys and girls undergoing cataract surgery was approximately equal (P = 0.110). However, in the cases of bilateral cataract, the proportion of boys was larger than girls (P = 0.028). More than half (62.3%) of the patients underwent surgery at the age of >3 years. The main presenting complaint was white pupils, accounting for 48.1% of cases. Total cataract was the most common morphologic type in all age groups. In total, 133 children out of 942 (14.1%) had a positive family history of congenital/developmental cataract. Strabismus and nystagmus were seen in 27.2% and 19.3% of the eyes, respectively. Additional ocular dysmorphology was found in 97 (10.3%) of patients. Coexisting systemic disease was found in 149 (15.8%) cases. Among syndrome-associated cataracts, Down syndrome accounted for the majority of cases.
CONCLUSION
High prevalence of total cataracts as well as frequent association with strabismus and nystagmus are likely to be the consequences of delayed presentation.
Topics: Male; Child; Female; Humans; Child, Preschool; Kazakhstan; Retrospective Studies; Cataract; Nystagmus, Pathologic; Strabismus; Pupil
PubMed: 36453339
DOI: 10.4103/ijo.IJO_939_22 -
Survey of Ophthalmology 2022Infantile cataracts remain one of the most treatable causes of lifelong visual impairment. While the chance of improving vision for children with infantile cataracts has... (Review)
Review
Infantile cataracts remain one of the most treatable causes of lifelong visual impairment. While the chance of improving vision for children with infantile cataracts has never been better, significant global and socioeconomic disparities still exist in their early management. Recent epidemiological studies reveal a stable prevalence of infantile cataracts in high-income countries and highlight challenges in determining the prevalence of infantile cataracts in low-income countries. Detailed descriptions of cataract morphology may inform us as to etiology, provide guidance with regards to surgical approach, and have prognostic value. Molecular genetics is providing new insights into the hereditary bases and potential systemic associations of infantile cataracts. For visually significant infantile cataracts requiring surgery to clear the visual axis, surgical techniques continue to evolve based on the experiences and research efforts of skilled teams worldwide. The most common complications of cataract surgery performed in infancy are visual axis opacification and, in about a third of patients, the long-term development of glaucoma. Children with unilateral cataracts generally see well given the presence of a healthy fellow eye. Better visual outcomes in operated eyes, however, are achieved in the setting of early presentation, bilateral infantile cataracts, absence of nystagmus or strabismus, and consistent amblyopia therapy. While intraocular lenses for infants less than 6 months can result in good visual outcomes, contact lenses may be preferred in situations in which they are available and practical. Many studies have demonstrated the benefits of early surgery for infantile cataract. We must strive for the continued evolution of technologies and strategies that have the potential to further improve these outcomes.
Topics: Cataract; Cataract Extraction; Child; Follow-Up Studies; Humans; Infant; Lens Implantation, Intraocular; Lens, Crystalline; Lenses, Intraocular; Retrospective Studies
PubMed: 35307324
DOI: 10.1016/j.survophthal.2022.03.005