3.8 Review

The Role of Gap Junctions Dysfunction in the Development of Cataracts: From Loss of Cell-to-Cell Transfer to Blurred Vision-Review

Related references

Note: Only part of the references are listed.
Article Biochemistry & Molecular Biology

Mechanical Stretch Activates TRPV4 and Hemichannel Responses in the Nonpigmented Ciliary Epithelium

Mohammad Shahidullah et al.

Summary: Our study found a mechanosensitive ion channel called TRPV4 and functional connexin hemichannels on the basolateral surface of the ocular nonpigmented ciliary epithelium (NPE). These channels respond to mechanical stimuli, such as cyclic stretch, and lead to the release of ATP and propidium iodide (PI), indicating hemichannel opening. TRPV4 and connexin mimetic peptide Gap 27 play important roles in this response, as their inhibition prevents ATP release and PI uptake. TRPV4-dependent connexin hemichannel opening acts as a mechanosensor that influences fluid secretion by the NPE.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Multidisciplinary Sciences

Protein kinase A activation alleviates cataract formation via increased gap junction intercellular communication

Yu Du et al.

Summary: Cataract is a major cause of blindness worldwide. The study found that protein kinase A (PKA) activation increases gap junction communication, reducing oxidative stress-induced cataracts and reactive oxygen species (ROS) levels. PKA activation also protects lens fiber cells from oxidative stress-induced death through hemichannel-mediated glutathione transport. Deletion of connexins, the proteins responsible for gap junctions, leads to increased lens opacity and reduced anti-oxidative stress gene expression. In summary, PKA activation via increased connexin channels alleviates cataracts by reducing ROS levels and cell death.

ISCIENCE (2023)

Article Pharmacology & Pharmacy

Patch clamp studies on TRPV4-dependent hemichannel activation in lens epithelium

Jose F. Ek-Vitorin et al.

Frontiers in Pharmacology (2023)

Review Biochemistry & Molecular Biology

Connexin Mutations and Hereditary Diseases

Yue Qiu et al.

Summary: Inherited diseases caused by connexin mutations affect multiple organs and share similar pathogenic mechanisms involving cellular proliferation and differentiation. Dominant mutations play a role in the onset of the diseases and gene therapy may not be effective for patients with these mutations. Complete loss or altered function of gap junctions and channels are also identified.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Cell Biology

Connexin Mutants Cause Cataracts Through Deposition of Apatite

Peter J. Minogue et al.

Summary: Cataracts, a common cause of blindness, are believed to develop from accumulation of damage to lens proteins. However, recent evidence suggests that calcium ion accumulation and precipitation of calcium-containing salts may also lead to cataracts. Studies on mutant mice with cataracts caused by connexin46 and connexin50 mutations found the presence of radio-dense minerals in the mutant lenses, suggesting a pathological mineralization process.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

Review Physiology

Loss of fiber cell communication may contribute to the development of cataracts of many different etiologies

Eric C. Beyer et al.

Summary: The lens circulation and intercellular coupling play important roles in the development of various types of cataracts and connexin mutations are a common cause. However, aging leads to decreased intercellular coupling and connexin levels, resulting in disruption of ionic homeostasis.

FRONTIERS IN PHYSIOLOGY (2022)

Article Biophysics

Molecular mechanisms underlying enhanced hemichannel function of a cataract-associated Cx50 mutant

Jun-Jie Tong et al.

Summary: The cataract-associated mutant Cx50T39R exhibits enhanced hemichannel currents and altered voltage-gating properties, leading to potential cytotoxicity. Coexpression of mutant T39R with wild-type Cx50 shows dominant effects, while coexpression with Cx46 increases hemichannel activity. In contrast, coexpression of wild-type Cx50 with Cx46 reduces hemichannel activity, suggesting a protective effect.

BIOPHYSICAL JOURNAL (2021)

Article Biochemistry & Molecular Biology

Connexin hemichannels regulate redox potential via metabolite exchange and protect lens against cellular oxidative damage

Yumeng Quan et al.

Summary: Our study reveals that Cx43 hemichannels (HCs) in lens epithelial cells play a crucial role in protecting the lens against oxidative stress by facilitating the exchange of oxidants and antioxidants, thereby maintaining redox homeostasis. Activation of Cx43 HCs by oxidative stress results in a reduction of intracellular reactive oxygen species (ROS) accumulation and regulation of anti-oxidative gene expression, contributing to preventing cataract formation during aging.

REDOX BIOLOGY (2021)

Review Biochemistry & Molecular Biology

Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis

Yumeng Quan et al.

Summary: The lens uses connexin channels to maintain its redox homeostasis, but oxidative stress may lead to dysfunction of gap junction channels and hemichannels, thereby inducing cataract formation.

ANTIOXIDANTS (2021)

Review Biochemistry & Molecular Biology

Connexin Mutants Compromise the Lens Circulation and Cause Cataracts through Biomineralization

Viviana M. Berthoud et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Article Ophthalmology

The human Descemet's membrane and lens capsule: Protein composition and biomechanical properties

Willi Halfter et al.

EXPERIMENTAL EYE RESEARCH (2020)

Article Biochemistry & Molecular Biology

Src Regulation of Cx43 Phosphorylation and Gap Junction Turnover

Joell L. Solan et al.

BIOMOLECULES (2020)

Article Ophthalmology

Identification and Functional Assessment of Age-Dependent Truncations to Cx46 and Cx50 in the Human Lens

Nefeli Slavi et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2016)

Article Ophthalmology

Calcium entry via connexin hemichannels in lens epithelium

Amritlal Mandal et al.

EXPERIMENTAL EYE RESEARCH (2015)

Article Ophthalmology

Number of People Blind or Visually Impaired by Cataract Worldwide and in World Regions, 1990 to 2010

Moncef Khairallah et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2015)

Article Cell Biology

Cx46 hemichannels contribute to the sodium leak conductance in lens fiber cells

Lisa Ebihara et al.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2014)

Article Biochemistry & Molecular Biology

Connexin 46 (Cx46) Gap Junctions Provide a Pathway for the Delivery of Glutathione to the Lens Nucleus

Nefeli Slavi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Review Physiology

Connexin hemichannels in the lens

Eric C. Beyer et al.

FRONTIERS IN PHYSIOLOGY (2014)

Review Pharmacology & Pharmacy

Connexin mutants and cataracts

Eric C. Beyer et al.

FRONTIERS IN PHARMACOLOGY (2013)

Review Biochemistry & Molecular Biology

Protein misfolding and aggregation in cataract disease and prospects for prevention

Kate L. Moreau et al.

TRENDS IN MOLECULAR MEDICINE (2012)

Article Biochemistry & Molecular Biology

Phosphorylation of Connexin 50 by Protein Kinase A Enhances Gap Junction and Hemichannel Function

Jialu Liu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2011)

Review Biology

Homeostasis in the vertebrate lens: mechanisms of solute exchange

Ralf Dahm et al.

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES (2011)

Review Biochemistry & Molecular Biology

Oxidative Stress, Lens Gap Junctions, and Cataracts

Viviana M. Berthoud et al.

ANTIOXIDANTS & REDOX SIGNALING (2009)

Article Biochemistry & Molecular Biology

Interplay between PKC and the MAP kinase pathway in Connexin43 phosphorylation and inhibition of gap junction intercellular communication

Solveig Sirnes et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2009)

Article Biochemistry & Molecular Biology

Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation

Puttur Santhoshkumar et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2008)

Article Ophthalmology

Functional characterization of a naturally occurring Cx50 truncation

Adam M. DeRosa et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2006)

Review Biochemistry & Molecular Biology

Temporal regulation of connexin phosphorylation in embryonic and adult tissues

TJ King et al.

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES (2005)

Article Biochemistry & Molecular Biology

An aberrant sequence in a Connexin46 mutant underlies congenital cataracts

PJ Minogue et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2005)

Article Ophthalmology

Regulation of aquaporin water permeability in the lens

K Varadaraj et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2005)

Review Ophthalmology

The lens: local transport and global transparency

RT Mathias et al.

EXPERIMENTAL EYE RESEARCH (2004)

Article Ophthalmology

Expression patterns for glucose transporters GLUT1 and GLUT3 in the normal rat lens and in models of diabetic cataract

BR Merriman-Smith et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2003)

Article Cell Biology

Loss of function and impaired degradation of a cataract-associated mutant connexin50

VM Berthoud et al.

EUROPEAN JOURNAL OF CELL BIOLOGY (2003)

Review Ophthalmology

Lens epithelial cell differentiation

AS Menko

EXPERIMENTAL EYE RESEARCH (2002)

Article Biochemistry & Molecular Biology

Functional role of the carboxyl terminal domain of human connexin 50 in gap junctional channels

X Xu et al.

JOURNAL OF MEMBRANE BIOLOGY (2002)

Article Cell Biology

Connexin46 mutations linked to congenital cataract show loss of gap junction channel function

JD Pal et al.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2000)