title: Nicotine accelerates diabetes-induced retinal changes.
abstract: OBJECTIVE
  To investigate the effects of nicotine on retinal alterations in early-stage diabetes in an established rodent model.
  
  
  METHODS
  Sprague-Dawley rats were examined using a combination of confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography to determine changes in retinal structure in response to nicotine exposure, diabetes and the combined effects of nicotine and diabetes. Diabetes was induced by a single injection of 65 mg/kg streptozotocin and nicotine injections were administered subcutaneously daily. Retinal thickness in the superior, inferior, nasal and temporal quadrants were determined based on the spectral domain optical coherence tomography (SD-OCT) volume scans (20° × 20°) centered on the optic disc. Segmentation of discrete retinal layers was performed on a subset of SD-OCT cross-sections to further examine changes in each treatment group. Survival of neurons within the ganglion cell layer (GCL) was assessed by confocal morphometric imaging.
  
  
  RESULTS
  The control group did not experience any significant change throughout the study. The nicotine treatment group experienced an average decrease in total retinal thickness (TRT) of 9.4 µm with the majority of the loss localized within the outer nuclear layer (ONL) as determined by segmentation analysis (p < 0.05). The diabetic group exhibited a trend toward decreased TRT while segmentation analysis of the diabetic retinopathy (DR) group revealed significant thinning within the ONL (p < 0.05). The combination of nicotine and diabetes revealed a significant increase of 8.9 µm in the TRT (p < 0.05) accompanied by a decrease in the number of GCL neurons.
  
  
  CONCLUSIONS
  We demonstrated significant temporal changes in retinal morphology in response to nicotine exposure, diabetes and with the combined effects of nicotine and diabetes. These findings may have implications in determining treatment strategies for diabetic patients using products containing nicotine, such as cigarettes, smokeless tobacco, electronic cigarettes or smoking cessation products.
authors.affiliation: Center for Biomedical Engineering .
authors.forename: Adam
authors.initials: A
authors.lastname: Boretsky
authors.forename: Praveena
authors.initials: P
authors.lastname: Gupta
authors.forename: Nima
authors.initials: N
authors.lastname: Tirgan
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Godley
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhang
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tilton
authors.forename: Massoud
authors.initials: M
authors.lastname: Motamedi
mesh_terms: D000818:Animals; D002470:Cell Survival; D018678:Cholinergic Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000175:diagnosis / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000503:physiopathology*; D005451:Fluorescein Angiography; D008297:Male; D018613:Microscopy, Confocal; D064847:Multimodal Imaging; D009538:Nicotine / Q000494:pharmacology*; D009887:Ophthalmoscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D055351:Retinal Neurons / Q000187:drug effects / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: D018678:Cholinergic Agents; D009538:Nicotine
keywords: Diabetes; SD-OCT; SLO; neurons; nicotine; retinal thickness