Fig 1.
Fig 1 shows the fundus images of human subjects with stage 4A (A) and 4B (B) ROP. The stages were classified according to ICROP (International classification of Retinopathy of Prematurity).
Fig 2.
Vitreous obtained from the human ROP and Control subjects were evaluated for the presence of the (A) total protein and (B) total collagen. No significant differences were observed between the groups. Data is presented as mean ±SEM.
Fig 3.
Protein concentration of RAS components and angiogenic factors.
Human vitreous of disease (n = 44) and control patients (n = 12) were subjected for the quantification of (A) VEGF- vascular endothelial growth factor, (B) HIF1α-Hypoxia inducible factor 1 alpha, (C) angiotensinogen, (D) ACE-Angiotensin Converting Enzyme, (E) ANG II- angiotensin II and (F) Renin. All concentrations were normalized as per mg/protein. Data is represented as mean ±SEM, significant difference found in comparison with respective control (***p≤0.001, **p≤0.01, *p≤0.05), using unpaired student t-test.
Fig 4.
FITC conjugated dextran retinal flat mount.
Arrows show the avascularised junction between the mid zone of retina and the ora serrata along with microaneurysm using FITC dextran labelling (A) Normal group- fully vascularised retina (B) Hyperoxia group- avascularised zone can be seen towards peripheral retina.
Fig 5.
Fig 4A is showing the significant increase in tortousity index of disease control as compared to normoxia (p≤0.01), whereas fig 4B is depicting the significant fall in the TI of treatment groups in comparison with disease control. Fig 4C & 4D tortousity index of veins in various groups, where no significant difference was observed. Data is represented as mean ±SEM, significant difference found in comparison with respective control (***p≤0.001, **p≤0.01, *p≤0.05), using unpaired student t-test (n = 9).
Fig 6.
‘b’ wave significantly decreased (*p≤0.01) in disease control group (6A). Fig 6B depicting the improved ‘b’ wave response in all treatment group in comparison with disease control. Fig 6C & 6D showing the ‘a’ wave response of various groups. Data is represented as mean ±SEM, significant difference found in comparison with respective control (***p≤0.001, **p≤0.01, *p≤0.05), using mann-whitney test (n = 9).
Fig 7.
Representative graphs for (A) electroretinogram, (B) oscillatory potential. Whereas (C1–6) represents (C1) disease control, (C2) normoxia, (C3) bevacizumab, (C4) lisinopril, (C5) telmisartan group fundus images.
Fig 8.
Oscillatory potential amplitude & latency.
Fig 8A represents Oscillatory potentials (OPs) timing of disease control (DC) and normal and 8B represents the timings of OPs of various treatment groups with comparison to DC. Fig 8D shows the significant elevation of OPs amplitude in normal as compared to DC and fig 8C represents the significantly increased amplitude of test groups in comparison with DC. Data is represented as mean ±SEM, significant difference found in comparison with respective control (***p≤0.001, **p≤0.01, *p≤0.05), using mann-whitney test (n = 9).
Fig 9.
Fig 9A shows the significant multiple folds up regulation of VEGF- vascular endothelial growth factor, HIF1α- Hypoxia inducible factor 1 alpha, angiotensinogen, ACE-Angiotensin Converting Enzyme, AT1 receptor and renin in disease control group in comparison to normal group. Fig 9B, 9C, 9D, 9E, 9F and 9G is representing the normalised expression of HIF 1 α, VEGF, renin, ACE, angiotensinogen and AT1 receptor in various test groups in comparison to disease control. Data is represented as mean ±SEM, significant difference found in comparison with respective control (***p≤0.001, **p≤0.01, *p≤0.05), using Rest (relative expression software tool). DC-disease control, BVZ-bevacizumab, LIS-lisinopril, TELM-telmisartan (n = 9).
Fig 10.
Levels of Lisinopril & Telmisartan.
Fig 10A shows the telmisartan levels and fig 10B shows the lisinopril levels in the plasma, vitreous and retina. Data is represented as mean ±SEM, significant difference found in comparison with respective control (***p≤0.001, **p≤0.01, *p≤0.05), using unpaired student t-test (n = 9).