A novel model of retinopathy of prematurity in normobaric hyperoxic conditions.
OBJECTIVE
To examine changes in retinal vasculature after treatment with different oxygen concentrations from common retinopathy of prematurity (ROP) models and to determine a novel and practical ROP model.


METHODS
A sample of 14 newborn Sprague-Dawley rats was used. The study group (n=7) was exposed to 95% oxygen for 4h per day followed by normoxic laboratory conditions for 20h. This cycle was repeated for 14d. The control group (n=7) was subjected to normobaric normoxic conditions. On postnatal day 14 (P14), the two groups were placed in room air for 7d. On P21, the two groups were examined using indirect ophthalmoscopy. All eyes were enucleated for immunofluorescence (IF) staining of the vasculature of retinas and analysis of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), placental growth factor (PLGF) in vitreous humor, and then the rats were sacrificed by decapitation. All procedures were repeated using another litter of 14 pups.


RESULTS
In the study group and under normobaric hyperoxic conditions, retinal neovascularization and peripheral avascular retina were determined in 85% of the rats through indirect ophthalmoscopic examination. Also IF staining of retina of the study group showed retarded peripheral vascular growth. The difference between the two groups for VEGF, HIF-1α and PLGF concentrations of vitreous humor was statistically significant (P=0.003, 0.007, 0.027 respectively).


CONCLUSIONS
Fluctuating oxygen concentrations are primarily responsible for retinal neovascularization. Our new ROP model is practical and applicable for all retinal neovascularization studies, considering the laboratory procedures.
Department of Medical Biochemistry, Gulhane Military Medical Academy, Ankara 06010, Turkey.
Taner
T
Ozgurtas
School of Medicine, Gulhane Military Medical Academy, Ankara 06010, Turkey.
Sercan
S
Tekin
Department of Medical Biochemistry, Diyarbakir Military Hospital, Diyarbakir 21100, Turkey.
Fatih
F
Yesildal
Department of Ophthalmology, Isparta Military Hospital, Isparta 32040, Turkey.
Umut
U
Karaca
Department of Biochemistry, Sirnak Military Hospital, Sirnak 73000, Turkey.
Fevzi Nuri
FN
Aydin
School of Medicine, Gulhane Military Medical Academy, Ankara 06010, Turkey.
Muhammed Talha
MT
Ugurlu
Department of Physiology, Gulhane Military Medical Academy, Ankara 06010, Turkey.
Mehmet
M
Ozler
Department of Ophthalmology, Gulhane Military Medical Academy, Ankara 06010, Turkey.
Hakan
H
Durukan
fundoscopy; hypoxia inducible factor-1 alpha; placental growth factor; retina staining; retinopathy of prematurity; vascular endothelial growth factor
Pediatrics. 2000 Feb;105(2):420-1
10654965
Can J Ophthalmol. 1990 Jun;25(4):186-9
2354394
Trans Am Ophthalmol Soc. 1942;40:262-84
16693285
Arch Ophthalmol. 1996 Oct;114(10 ):1219-28
8859081
Pediatrics. 1985 Sep;76(3):339-44
2863804
Lancet. 2013 Oct 26;382(9902):1445-57
23782686
Retina. 2010 Apr;30(4 Suppl):S24-31
20224475
Invest Ophthalmol Vis Sci. 1996 Feb;37(2):300-11
8603834
Invest Ophthalmol Vis Sci. 1994 Jan;35(1):101-11
7507904
Invest Ophthalmol Vis Sci. 1995 Sep;36(10 ):2063-70
7657545
Am J Ophthalmol. 1953 Nov;36(11):1511-22
13104558
J Cell Physiol. 2000 Sep;184(3):301-10
10911360
J Perinatol. 2004 Feb;24(2):82-7
14762452
Pediatrics. 1988 Aug;82(2):193-8
3399291
Pediatr Res. 1994 Dec;36(6):724-31
7898981
Acta Ophthalmol. 2014 Feb;92(1):2-20
23617889
Prog Retin Eye Res. 2010 Nov;29(6):500-19
20488255
Arch Dis Child Fetal Neonatal Ed. 2013 Mar;98(2):F170-4
22209748
Am J Ophthalmol. 1986 Jul 15;102(1):1-6
3728608
Arch Ophthalmol. 2010 May;128(5):589-95
20457980
Eur J Med Chem. 2012 Mar;49:24-40
22305612
Graefes Arch Clin Exp Ophthalmol. 2011 Apr;249(4):537-46
21104270
J AAPOS. 2008 Jun;12(3):221-2
18396079
Pediatrics. 1999 Sep;104(3):e26
10469809
PLoS One. 2008 Jul 23;3(7):e2748
18648503
N Engl J Med. 2011 Feb 17;364(7):603-15
21323540
Graefes Arch Clin Exp Ophthalmol. 1993 Mar;231(3):151-6
8462887
Invest Ophthalmol Vis Sci. 1993 Mar;34(3):576-85
8449677
Int Ophthalmol Clin. 1977 Summer;17(2):121-35
577204
Invest Ophthalmol Vis Sci. 1994 Jul;35(8):3169-77
8045712
Acta Ophthalmol. 2012 May;90(3):277-86
21812942
Circ Res. 2013 Oct 12;113(9):1076-86
23897694
Br J Ophthalmol. 1954 Jul;38(7):397-432
13172417
Early Hum Dev. 2008 Feb;84(2):77-82
18234457