Proliferatif diyabetik retinopati patogenezinde vitreus içi mikroRNA ve midkine düzeylerinin rolü
The role of intervitreus microrna and midkin levels in pathogenesis of proliferative diabetic retinopathy
Yazar: İRFAN AKARAY
Danışman: DOÇ. DR. SADIK ALTAN ÖZAL
Trakya Üniversitesi / Tıp Fakültesi / Göz Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2021
Konu: Göz Hastalıkları = Eye Diseases
Dizin: Diabetes mellitus = Diabetes mellitus ; Diabetik retinopati = Diabetic retinopathy ; Midkin = Midkine ; Mikro RNA = Micro RNA ; RNA = RNA ; Vasküler endotel büyüme faktörleri = Vascular endothelial growth factors ; Vitreus = Vitreous

Özet:
Proliferatif diyabetik retinopatide vitreus içi mikroRNA, vasküler endoteyal büyüme faktörü ve Midkine düzeylerinin patogenezdeki rolünü araştırmak.
Çalışmamız proliferatif diyabetik retinopatiye tanısı almış 26 hasta, diyabetik hastalığı olmayan kontrol grubu olarak 26 olgu dahil edilmiştir. Hastaların cinsiyet, yaş, Hba1c düzeyleri, Vasküler endoteyal büyüme faktörü ve Midkine düzeyleri Enzyme-Linked ImmunoSorbent Assay (ELİSA) ile tespit edildi. MiR-124, miR-20b, miR-200b, miR-19a, miR-27a, miR-126 ve miR-146a düzeyleri kantitatif polimeraz zincir reaksiyonu (qPCR) ile ekspresse edildi.
Çalışma grubunda 26 hastanın 18 (%69.2) erkek, 8 (%30.8) kadın hasta, kontrol grubunda 19 (%73.0) erkek, 7 (%27.0) kadın hasta vardı (P=0.56). Çalışma grubun yaş ortalaması; 57.2±8.9, kontrol grubun yaş ortalaması; 58.3±12.9 idi (P=0.72).  Hba1c düzeyleri çalışma grubunda 9.56±1.40 mmol/mol, kontrol grubunda 5.28±0.76 mmol/mol (P=0.00). MiR-124, çalışma grubunda 1.96 kat artmış olduğu saptadık (P=0.04). MiR-126, çalışma grubunda 2.14 kat artmış olduğunu bulduk (P=0.00). MiR-19, çalışma grubunda 1.59 kat artmış olduğu saptadık (P=0.13). MiR-20b, çalışma grubunda 1.55 kat artmış olduğunu bulduk (P=0.06). MiR-27a, çalışma grubunda 1.31 kat azaldığı saptadık (P=0.64). Mir-146a düzeylerin ise çalışma ve kontrol grubunda eşit oranda bulduk (P=0.92). MiR-200b değerin çalışma grubunda 2.99 kat azalmış olduğunu saptadık (P=0.01). Midkine düzeylerin çalışma grubunda 371.45±72.58 pg/ml kontrol grubunda 319.29±81.22 pg/ml ölçüldü (p=0.02). Vasküler endotelyal büyüme faktör-A düzeylerin çalışma grubunda 6.29±0.98 ug/ml, kontrol grubunda 5.34±1.32 ug/ml hesapladık (p=0.00).
Sonuç olarak proliferatif diabetik retinopatide miR-124 ile miR-126 artması ve miR-200b değerin azalması ile vitreusta çok az çalışılan midkine düzeylerin azalması proliferatif diyabetik retinopati patogenezinde önemli rol alabileceği, hastalığın tanı, tedavi ve izleminde biobelirteç olarak kullanılabileceğini vurguladık.
Anahtar kelimeler: Diabetik Retinopati, Midkine, mikroRNA, VEGF-A, Vitreus

Abstract:
THE ROLE OF INTERVITREUS MicroRNA AND MIDKIN LEVELS IN PATHOGENESIS OF PROLIFERATIVE DIABETIC RETINOPATHY
SUMMARY

To analyze the role of intravitreal microRNA, vascular endothelial growth factor and Midkine levels in the pathogenesis of diabetic retinopathy. 
This study was conducted with 26 patients diagnosed with diabetic retinopathy and 26 patients with no diabetes as a control group. The data of gender, age and HbA1c results were obtained from the medical records of the patients and vascular endothelial growth factor and Midkine levels were measured with Enzyme-Linked ImmunoSorbent Assay (ELISA). The levels of miR-124, miR-20b, miR-200b, miR-19a, miR-27a, miR-126 and miR-146a levels were expressed by quantitative polymerase chain reaction (qPCR).
In the study group of 26 patients, 18 (%69.2) patients were male, 8 (%30.8) were female and in the control group of 26 non-diabetic patients, 19 (%73.0) were male, 7 (%27.0) were female (p=0.56). The mean age for the study group was standing at 57.2±8.9 years while it was 58.3±12.9 years as for the control group (p=0.72). HbA1c levels revealed to be averagely 9.56±1.40 mmol/mol for the study group and 5.28±0.76 mmol/mol for the control group (p<0.001). . MiR-124 levels was found out to be elevated 1.96 times as much as the control group in the study group (p=0.04) and MiR-126 was 2.14 times as much (p<0.001). MiR-124 levels was found out to be elevated 1.96 times as much as the control group in the study group (p=0.04) and MiR-126 was 2.14 times as much (p<0.001). MiR-19 level was elevated 1.59 times as much (p=0.13) and MiR-20b was increased 1.55 times as much (p=0.06). MiR-27a was also increased 1.31 times as much as the control group (p=0.64) and MiR-146a levels remained the same as the control group (p=0.92). MiR-200b level was found out to be increased 2.99 times as much as the control group (p=0.01). Midkine levels were measured as 371.45±72.58 pg/ml in the study group alongside the Midkine level of 319.29±81.22 pg/ml for the control group (p=0.02). Vascular endothelial growth factor-A was seen to be 6.29±0.98 ug/ml in the study group and 5.34±1.32 ug/ml in the control group (p<0.001).
In conclusion, in proliferative diabetic retinopathy, the increase of miR-124 and miR-126 and the decrease of miR-200b value and the decrease in midkine levels, which have been studied very little in the vitreous, may play an important role in the pathogenesis of proliferative diabetic retinopathy and can be used as a biomarker in the diagnosis, treatment and follow-up of the disease.
	Keywords: Diabetic Retinopathy, Midkine, microRNA, VEGF-A,  Vitreus