Gap junction protein connexin43 (GJA1) in the human glaucomatous optic nerve head and retina

Kerr, Nathan M.; Johnson, Cort; Green, Colin; Danesh‐Meyer, Helen V.

doi:10.1016/j.jocn.2010.06.002

Cited by 38 publications

(36 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Secondary cell death mediated by neuronal gap junctions has been implicated previously in retinal cell loss associated with a number of degenerative conditions, including retinitis pigmentosa, ischemia, excitotoxicity, and glaucoma (Ripps, ; Malone et al, ; Kerr et al, ; Danesh‐Meyer et al, ; Akopian et al, ). Interestingly, a low vulnerability of ChAT‐IR and glycinergic ACs has been reported under a number of pathological situations (Williams et al, ; Moon et al, ; Bernstein and Guo, ; Akopian et al, ).…”

Section: Discussionmentioning

confidence: 99%

Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas

Akopian

Kumar

Ramakrishnan

et al. 2016

J of Comparative Neurology

View full text Add to dashboard Cite

We determined whether the structural and functional integrity of amacrine cells (ACs), the largest cohort of neurons in the mammalian retina, are affected in glaucoma. Intraocular injection of microbeads was made in mouse eyes to elevate intraocular pressure as a model of experimental glaucoma. Specific immunocytochemical markers were used to identify AC and displaced (d)ACs subpopulations in both the inner nuclear and ganglion cell layers, respectively, and to distinguish them from retinal ganglion cells (RGCs). Calretinin- and γ-aminobutyric acid (GABA)-immunoreactive (IR) cells were highly vulnerable to glaucomatous damage, whereas choline acetyltransferase (ChAT)-positive and glycinergic AC subtypes were unaffected. The AC loss began 4 weeks after initial microbead injection, corresponding to the time course of RGC loss. Recordings of electroretinogram (ERG) oscillatory potentials and scotopic threshold responses, which reflect AC and RGC activity, were significantly attenuated in glaucomatous eyes following a time course that matched that of the AC and RGC loss. Moreover, we found that it was the ACs coupled to RGCs via gap junctions that were lost in glaucoma, whereas uncoupled ACs were largely unaffected. Our results suggest that AC loss in glaucoma occurs secondary to RGC death through the gap junction-mediated bystander effect. J. Comp. Neurol., 2016. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas

Akopian

Kumar

Ramakrishnan

et al. 2016

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…[12][13][14] In human and rat retinae, Cx43 is mainly expressed in Müller cells, astrocytes, vascular endothelium, and retinal pigment epithelium. [15][16][17][18] Increased Cx43 immunoreactivity has been shown in human retina associated with glaucoma 19 and following optic nerve injury. 20 In a light-damaged albino rat, Cx43 expression is significantly elevated in the choroid within 6 hours following light damage.…”

mentioning

confidence: 99%

Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model

Guo

Nor

Danesh‐Meyer

et al. 2016

Invest. Ophthalmol. Vis. Sci.

Self Cite

View full text Add to dashboard Cite

PURPOSE. Drugs that regulate connexin43 (Cx43) gap junction channels can reduce the spread of injury and improve functional outcomes after nervous system trauma. In the eye, Cx43 expression increases in the choroid following light damage. The aim of this study was to investigate whether Cx43 hemichannel block could preserve retinal function postinjury. RESULTS. Light-damaged rat eyes had (1) reduced neuronal responses in both the rod and cone pathways and (2) marked inflammatory responses in the choroid and retina. Peptide5 significantly preserved function of photoreceptoral and postphotoreceptoral neurons in these animals. This was evident 24 hours after injury and 2 weeks later, as shown by improved mixed a-wave and mixed b-wave amplitudes, isolated rod PII and PIII amplitudes, and cone PII responses when compared with sham-treated controls. Retinal thinning and inflammation were also significantly reduced in Peptide5-treated eyes when compared with sham-treated controls.CONCLUSIONS. Blocking Cx43 hemichannels after light damage can significantly improve functional outcomes of neurons in both the rod and cone photo-transduction pathways in the light-damaged animal model, likely by reducing choroid inflammation and suppressing the glial-mediated inflammatory response. These data may have relevance for the treatment of conditions such as diabetic retinopathy and age-related macular degeneration.

show abstract

“…Upregulation of Cx43 gap junctions has been found in a number of chronic central nervous system diseases and acute insults including mesial temporal lobe epilepsy [39], Huntington's disease [40], glaucoma [41], ischemic stroke [42][43][44], trauma [7,9,45], and retinal ischemia [45,46]. Increased Cx43 expression has also been seen in senile plaques in post-mortem brains of patients with Alzheimer's disease [47].…”

Section: Connexins In the Brainmentioning

confidence: 99%

A Key Role for Connexin Hemichannels in Spreading Ischemic Brain Injury

Davidson

Green²,

Bennet³

et al. 2013

Current Drug Targets

View full text Add to dashboard Cite

Brain damage resulting from cerebral ischemia remains a significant problem at all stages of life. In adults, ischemic stroke is the third leading cause of death and the leading cause of disability in the developed world. In term newborns, moderate to severe brain damage after hypoxia-ischemia (HI) occurs in 1-3 per 1000 live births. One of the most striking features of HI injury is that after initial recovery of cellular oxidative metabolism, there is a delayed, 'secondary' mitochondrial failure that spreads over time from the most severely damaged areas outwards, into previously undamaged regions. This secondary failure is accompanied by transient seizure activity and cytotoxic edema. The specific mechanisms of this spread are poorly understood, but it is at least partly associated with spreading waves of depression that can trigger cell death in neighboring uninjured tissues. The waves are propagated through cell-cell communication via gap junction channels (the so called "bystander effect"). It has recently been proposed that unopposed connexin hemichannels (connexons) also play a significant role by mediating release of paracrine molecules that in turn propagate cell death messages by releasing intracellular mediators such as ATP, NAD(+), or glutamate or by abnormally prolonged opening to allow cell edema. There is increasing evidence that connexin hemichannels contribute to injury after many neural insults and that it is possible to significantly reduce the spread of damage after injury by suppressing the induction or activity of the connexin proteins that form hemichannels.

show abstract

Gap junction protein connexin43 (GJA1) in the human glaucomatous optic nerve head and retina

Cited by 38 publications

References 69 publications

Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas

Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas

Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model

A Key Role for Connexin Hemichannels in Spreading Ischemic Brain Injury

Contact Info

Product

Resources

About