Boretsky Adam, Gupta Praveena, Tirgan Nima, Liu Rong, Godley Bernard F, Zhang Wenbo, Tilton Ronald G, Motamedi Massoud
Center for Biomedical Engineering .
Curr Eye Res. 2015 Apr;40(4):368-77. doi: 10.3109/02713683.2014.924147. Epub 2014 Jun 9.
To investigate the effects of nicotine on retinal alterations in early-stage diabetes in an established rodent model.
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.
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.
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.
在已建立的啮齿动物模型中研究尼古丁对早期糖尿病视网膜病变的影响。
使用共焦扫描激光检眼镜和光谱域光学相干断层扫描相结合的方法对Sprague-Dawley大鼠进行检查,以确定视网膜结构因尼古丁暴露、糖尿病以及尼古丁与糖尿病联合作用而发生的变化。通过单次注射65mg/kg链脲佐菌素诱导糖尿病,并每天皮下注射尼古丁。基于以视盘为中心的光谱域光学相干断层扫描(SD-OCT)容积扫描(20°×20°)确定上、下、鼻侧和颞侧象限的视网膜厚度。对一部分SD-OCT横截面进行离散视网膜层分割,以进一步检查每个治疗组的变化。通过共焦形态计量成像评估神经节细胞层(GCL)内神经元的存活情况。
在整个研究过程中,对照组未出现任何显著变化。尼古丁治疗组的视网膜总厚度(TRT)平均减少了9.4μm,通过分割分析确定,大部分厚度损失位于外核层(ONL)(p<0.05)。糖尿病组的TRT有下降趋势,而糖尿病视网膜病变(DR)组的分割分析显示ONL明显变薄(p<0.05)。尼古丁与糖尿病联合作用导致TRT显著增加了8.9μm(p<0.05),同时GCL神经元数量减少。
我们证明了视网膜形态因尼古丁暴露、糖尿病以及尼古丁与糖尿病联合作用而发生显著的时间变化。这些发现可能对确定使用含尼古丁产品(如香烟、无烟烟草、电子烟或戒烟产品)的糖尿病患者的治疗策略具有启示意义。