title: Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention.
abstract: OBJECTIVE
  Examining the Retinal Renin Angiotensin System (RRAS) in the ROP neonates and analyzing the possibility of modulating the RRAS to prevent the progression in Oxygen Induced Retinopathy (OIR) model.
  
  
  METHODS
  Vitreous of ROP patients (n = 44, median age 5.5 months) was quantified for RRAS components, VEGF, HIF-1α and compared with age matched control. The involvement of RRAS in ROP was tested in the rat model of OIR and compared with normoxia. Expressions of RAS components, VEGF and HIF-1α in retina were analyzed using qPCR and retinal structure and function was also analyzed. Effect of Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) was evaluated and compared with Bevacizumab which served as a positive control. Drug penetration into retina was confirmed by liquid chromatography coupled ESI-tandem mass spectroscopy (LC-MS/MS).
  
  
  RESULTS
  Multifold increase in the expression of RAS components in human vitreous and rat retina showed their involvement in ROP. ERG & fundus studies in OIR revealed the altered function of retina and were successfully prevented by ARB (telmisartan), ACEI (lisinopril) and bevacizumab. Retinal analysis revealed the presence of ACEI and ARB in their therapeutic levels.
  
  
  CONCLUSIONS
  This study for the first time demonstrates the upregulated level of RAS components in human ROP vitreous and further that the pharmacological intervention in RRAS can functionally and structurally preserve retina against the progression of ROP in the OIR model.
authors.affiliation: Dept. Of Ophthalmology, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Nath
authors.affiliation: Dept. Of Ophthalmology, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Parijat
authors.initials: P
authors.lastname: Chandra
authors.affiliation: Dept. Of Ocular pharmacology, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Nabanita
authors.initials: N
authors.lastname: Halder
authors.affiliation: Dept. Of Biophysics, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Baskar
authors.initials: B
authors.lastname: Singh
authors.affiliation: Dept. Of NICU, Pediatrics, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Deorari
authors.affiliation: Dept. Of Ophthalmology, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Dept. Of Ophthalmology, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Rajvardhan
authors.initials: R
authors.lastname: Azad
authors.affiliation: Dept. Of Ocular pharmacology, Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical sciences, New Delhi, India.
authors.forename: Thirumurthy
authors.initials: T
authors.lastname: Velpandian
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D004596:Electroretinography; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000150:complications; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012160:Retina / Q000000981:diagnostic imaging; D012178:Retinopathy of Prematurity / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen