title: Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in a Light-Damaged Albino Rat Model.
abstract: 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.
  
  
  
  Light damage was induced by exposure of adult albino Sprague-Dawley rats to 2700 Lux light for 24 hours. Intravitreal injections of a Cx43 mimetic peptide hemichannel blocker, Peptide5, or sham were administered 2 hours after the onset and at the end of the light damage period. Retinal function was assessed by electroretinogram and inflammatory responses in the choroid and retina were assessed using immunohistochemistry (ionized calcium binding adaptor molecule 1 [Iba-1], leukocyte common antigen [CD45], glial fibrillary acidic protein [GFAP]).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: School of Optometry and Vision Science, University of Auckland, Auckland, New Zealand 2New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Cindy X
authors.initials: CX
authors.lastname: Guo
authors.affiliation: School of Optometry and Vision Science, University of Auckland, Auckland, New Zealand 2New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Mohd N
authors.initials: MN
authors.lastname: Mat Nor
authors.affiliation: New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand 3Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
authors.forename: Helen V
authors.initials: HV
authors.lastname: Danesh-Meyer
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia.
authors.forename: Kirstan A
authors.initials: KA
authors.lastname: Vessey
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Australia.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Fletcher
authors.affiliation: Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: O'Carroll
authors.affiliation: School of Optometry and Vision Science, University of Auckland, Auckland, New Zealand 2New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Acosta
authors.affiliation: New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand 3Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Green
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D040761:Biomimetic Materials / Q000008:administration & dosage; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018031:Connexin 43 / Q000008:administration & dosage* / Q000096:biosynthesis; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D058449:Intravitreal Injections; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008027:Light / Q000009:adverse effects; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C100745:Aif1 protein, rat; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D018031:Connexin 43; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D017493:Leukocyte Common Antigens; C516771:Ptprc protein, rat