| Research background:Parkinson's disease?PD?is the second most common neurodegenerative disorder,and visual problems is one of the non-motor symptoms of Parkinson's disease[1,2].82%of PD patients have at least one visual symptom,which seriously affects the patient's quality of life,but but it did not attracted the attention of patients and clinicians[3,4].In recent years,researches have found that retinal changes may be the structural basis of visual impairment.Speculated that the misfolding and abnormal aggregation of?-syn in the retina may be the pathological basis of retinal changes,but the related mechanisms are little studied.Therefore,we used optical coherence tomography?OCT?,a non-invasive bioimaging technology that can perform in vivo retinal imaging to evaluate the retinal morphological changes in PD patients.We observed the retinal function changes in patients with visual field inspection characteristics,and provided reliable objective parameters for visual impairment[10].Then,rotenone subcutaneous injection successfully induced PD model to study the expression and distribution of?-syn in the retina of animal models,and provided pathological basis for retinal changes in PD patients.Research purpose:To summarize the characteristics of retinal structure and function changes in PD patients,analyze the relationship between retinal parameters and disease severity,and determine whether OCT can be a simple and reliable method for early screening of visual dysfunction in PD.At the same time,through animal experiments,we will further clarify the role of?-syn in pathological changes of the retina,and provide evidence for the pathogenesis of Parkinson's disease visual impairment.Materials and Methods:1.Clinical study of retinal morphological changesWe recruited in our department of Neurology from June 2018 to November 2019.There were 31 PD patients?62 eyes?and 32 normal controls?64 patients?.All subjects required eye examination,clinical evaluation,and collection of general clinical data.The OCT examination included peripapillary retinal nerve fiber layer?pRNFL??including average thicknesses,superior,inferior,nasal,and temporal?and macular retina scans.Compared the differences between the retinal parameters in PD patients and controls.Visual field examination recorded the mean deviation and visual field index.ROC curve analysis was performed using GraphPad Prism6 software and Spearman rank correlation analysis was performed using STATA15.0 software.2.Animal experiments with changes in retinal pathological changesTwenty SPF male Sprague-Dawley rats were selected,and randomly divided into PD group?n=10?and control group?n=10?.The rats were injected subcutaneously in the neck and back,rotenone and sunflower oil emulsion in the PD group,and sunflower oil in the control group.The weight,behavioral changes,and behavioral scores were recorded daily for 81 days.Two groups were randomly selected for immunohistochemical detection of tyrosine hydroxylase?TH?positive cells in the substantia nigra region of rats,and the models were identified.The morphological changes of the retinas of the two groups of rats were observed by hematoxylin-eosin staining,and the expression and distribution of?-syn in the retinas of animal models were detected by immunofluorescence.Results:1.Baseline characteristics of subjects in the clinical studies involved in retinal morphological changesA total of 31 patients?62 eyes?were included in the PD group,and 32 patients?64eyes?were included in the control group.The majority of patients in the PD group were in the early stages of the disease.The average UPDRS III score was?28.68±15.57?points,the average H&Y scale was?2.35±0.70?grade,and the average disease duration was?3.58±2.56?years.There were no significant differences in gender,age,intraocular pressure,drinking,smoking,education,and occupation between the control group and the PD group?P>0.05?.2.Retinal morphological and functional changes in PD patientsThere are morphological changes in the retina of PD patients,mainly in the macular area.Compared with the control group,the macular volume of PD group was reduced.The macular fovea thickness,macular retinal thickness,and ganglion cell complexes?superior,inferior,and average thickness?were significantly thinner in PD patients than controls.The inner ring of macular retinal thickness?superior,inferior,nasal and temporal?and the outer ring of macular retinal thickness?superior,nasal and temporal?were thinner in PD patients than those in controls.There was no significant difference in the thickness of pRNFL?superior,inferior,nasal,temporal,and average thickness?between the two groups?P>0.05?.Patients with PD had visual field hypofunction.Compared with the control group,the visual field index was increased,and the mean deviation was decreased.The results of ROC curve analysis showed that the retinal parameters had better diagnostic value,and mainly in the inner ring of macular retinal thickness.3.Correlation between retinal parameters and clinical H&Y,UPDRS?scores and duration of disease in patients with Parkinson's disease.In terms of retinal morphology in PD patients,the H&Y scale was negatively correlated with macular foveal thickness,macular volume,and macular retinal thickness in male patients.The macular retinal thickness in the inner rings of quadrants?superior,inferior,nasal,and temporal?in female patients and the outer rings of quadrants?superior,inferior,nasal?in male patients were negatively correlated with H&Y.The UPDRS?scores was positively correlated with the thickness of the superior pRNFL in female patients.In terms of retinal function in PD group,the visual field index was negatively correlated with H&Y scale and UPDRS?scores,and the mean deviation was positively correlated with UPDRS?scores.There was no correlation between retinal morphological and function parameters and disease duration in PD patients?P>0.05?.4.Rotenone Parkinson's disease rat model of retinal morphologyThe results showed that the thickness of the retina,ganglion cell layer,inner nuclear layer,inner reticular layer and outer nuclear layer of the model rats in PD patients were thinner than those in controls,and all were statistically significant?P<0.05?.There was no significant difference in the thickness of the outer plexiform layer in the retina compared with the control group?P>0.05?.5.?-syn expression in the retina of rotenone parkinsonism ratsRetinal?-synuclein deposits in rotenone-induced Parkinson's disease rats,which are mainly distributed in the inner retinal layer,inner reticular layer and ganglion cell layer and?-synuclein aggregation were found in the ganglion cell layer and outer plexiform layer.Conclusion:1.OCT can be used to evaluate the morphological changes of the retinal structure of PD patients and provide reliable objective parameters and predictive value.2.The retinal morphological and functional characteristics of PD patients were as follows:thinned the thickness of macular retina,reduced the macular volume,and decreased the visual field function were observed;3.H&Y scale is negatively correlated with retinal parameters of the macular region and functional parameters.UPDRS?scores was positively correlated with pRNFL and mean deviation.The duration of disease was not related to retinal morphological and functional parameters;4.The retina of rotenone-induced Parkinson's disease rats were thinned and?-synuclein aggregation were found in the ganglion cell layer and outer plexiform layer. |
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