Objective To explore the effect of polycythemia on retinopathy of prematurity (ROP). Methods The clinical data of 262 premature cases was analyzed retrospectively in Xi'an Children Hospital from January 2005 to January 2009. Polycythemia was found in 46 cases (17.56%), including 27 males and 19 females. In 216 infants without polycythemia (82.46%), 155 were male and 61 were female. The difference of the birth weight (t=0.730, P=0.466), gestational age (t=1.603,P=0.110), oxygen inhalation numbers (chi;2=0.04,P＞0.90) and times (t=1.225,P=0.223), and concentration (t=1.823,P=0.071) between polycythemia group and no polycythemia group were not significant. In order to diagnose ROP, the ocular fundus of all premature infants was examined with binocular indirect ophthalmoscope,and the stage of ROP was assessed.Results In all the premature infants,ROP was found in 120 cases (45.80%). In 46 cases of polycythemia, ROP was found in 25 cases (54.34%); in 216 infants without polycythemia, ROP was found in 95 cases (43.98%); the difference of ROP incidence between the two groups was not significant (chi;2=1.64, Pgt;0.1).In 120 ROP patients, 104 cases (86.67%) with ROP＜3 stage and 16 cases (13.33%) with ROP ge;3 stage were found. In 25 ROP patients with polycythemia, 18 cases (72.00%) with ROP ＜3 stage and 7 cases (28.00%) with ROP ge;3 stage were found. In 95 ROP patients without polycythemia, 86 cases (90.53%) with ROP ＜3 stage and 9 cases (9.47%) with ROP ge;3 stage were found. The difference of the incidence of ROP ＜and ge;3 stage between the two group was significant (chi;2=4.38, Plt;0.05). In 120 cases of ROP, prethreshold retinopathy was found in 106 cases (88.33%), while threshold and post-threshold retinopathy was in 14 cases (11.67%). In 25 ROP patients with polycythemia, prethreshold retinopathy was found in 19 cases (76.00%), and threshold and post-threshold retinopathy was in 6 cases (24.00%).In 95 ROP infants without polycythemia, pre-threshold retinopathy was found in 87 cases (91.58%),while threshold and post threshold retinopathy was in 8 cases (8.42%).The difference of the incidence of ROP with prethreshold, and threshold and post-threshold retinopathy between the two groups was not significant (chi;2=3.27,P＞0.05).Conclusion Polycythemia may not affect the incidence of ROP,but impact on the severity of ROP.
Objective To determine the association between the geneti c polymorp hisms of vascular endothelial growth factor (VEGF) gene and the prognosis for retinopathy of prematurity (ROP) in Chinese. Methods Twenty infants with threshold ROP who had undergone retinal photocoagulation were in the treated group and 20 infants with self-regressed ROP without any treatment were in the control grou p . In the two groups, all the infants had oxygen-breathing history and the sex a n d gestational age were all suitable to be compared, except birth weight. Polymer ase chains reaction-restriction fragment length polymorphism was used to determine the frequencies of VEGF genes in the two groups. Results The frequencies of +405C allele were higher in the treated group than those in the control group (P＜0.05). The frequencies of the VEGF-460T/C and +936C/T ploymorphisms were similar in both groups (P＞0.05). Conclusions The +4 05C/G ge netic polymorphisms of VEGF may correlate to the prognosis of ROP. The carriers of +405CC allele are more susceptible to ROP.
Objective To learn the screening results of retinopathy o f prematur ity (ROP) of the preterm infants in three hospitals in Shenzhen. Metho ds From Jan. 2004 to Jan. 2007, 1372 preterm infants (2744 eyes) with birth weight lt;200 0 g or but the ones having severe systemic disease in Shenzhen People's Hospita l, Shenzhen Maternity and Child Healthcare Hospital and Shenzhen Eye Hospital we re screened for ROP with binocular indirect ophthalmoscope and (or) widefield digital pediatric retinal imaging system (RetCamII). Cryotherapy or laser photoco agulation was performed if threshold or pre-threshold type I ROP was found. All preterm infants were followed up until retina is completely vascularized or the disease regressed. Results In all the infants, 218 cases (436 eyes) (15.9％) developed ROP, including 190 eyes (6.9％) suffering from threshold or pre-threshold type 1 ROP, 16 eyes (0.6％) from stage 4 or stage 5, and 230 eyes (8.4％) from stages below threshold or pre-threshold type 1 ROP. There were 435 infants ( 870 eyes) (31.7%) with BW of 1500g or less, in which 236 eyes (27.1％) developed ROP, including 126 eyes (14.5％) suffering from threshold or pre-threshold type 1 ROP, 10 eyes (1.1％) from stage 4 or stage 5, and 100 eyes (11.5％) from stages below threshold or pre-threshold type 1 ROP. There were 137 infants 274 eyes (10%) with BW of 1250g or less, in which 108 eyes (39.4％) developed ROP, including 60 eyes (21.9％) suffering from th reshold or pre-threshold type 1 ROP, 4 eyes (1.4％) from stage 4 or stage 5, and 44 eyes (16％) from stages below threshold or pre-threshold type 1 ROP. Th eincidence of ROP（chi;2=60.43，Plt;0.001）, the incidence of threshold or pre-threshold type 1 ROP（chi;2=46.82，Plt;0.001）and the incidence of below threshold or pre-threshold type 1 ROP （chi;2=10.71，P=0.005）among the total group, BWle;1500g group and BWle;1250g group had statistical differences. Conclusions The incidence of ROP in the three hospitals in Shenzhen was lower. However, the incidence of severe ROP (threshold or pre-threshold type 1 ROP) was higher. Birth weight is an important factor to affect ROP incidence.
Objective To investigate the effect of inducible nitric oxide synth ase (iNOS) or cyclooxygenase－2 (COX－2) on retinal neovascularization and its possible mechanism in oxygen－induced retinopathy （OIR） mouse model. Methods Retinal neovascularization was induced by oxygen with different concentration. The expression of iNOS, COX－2, matrix metalloproteinases 2 (MMP－2) and vascular end othelial growth factor (VEGF) in the retinae of experimental animals were analyzed by immunohistochemistry, realtime polymerase chain reaction and western blotting technologies. Results The inhibition of COX－2 or iNOS obviously attenuated retinal neovascularization and decreased the expression of VEGF and MMP－2. The iNOS inhibition decreased COX－2 expression, and vice versa. Conclusions COX－2 and iNOS may play a role in retinal neovascularization in OIR mouse model, which may act by regulating the expression of VEGF and MMP－2.
Objective To observe the expression of erythropoietin (EPO) and its receptor (EPOR) mRNA and protein levels in retinae of mice with oxygen-induced retinopathy, and to evaluate the effect of EPO and EPOR in retinal vascular develo pment and in the occurrence and development of oxygen-induced retinopathy. Methods One hundred and thirty-two 7-day-old C57BL/6J mice were divided into two g rou ps: normal control group (control group) and oxygen-induced retinopathy group (experimental group). The proliferative neovascular response was estimated by obse rving the vascular pattern in adenosine diphosphatease (ADPase) stained retina flat-mounts by executing 6 mice in each group at the 12th, 15th, and 17th day, respectively. The expression of EPO, EPOR mRNA was determined by reverse transcription-polym erase chain reaction (RT-PCR), and the protein levels of EPO and E PO R were determined by immunohistochemistry. RT-PCR and immunohistochemistry were done every other day from the 7th to the 21st day. Results In the control group, retinal vascularization was found. In the experimental group, the large vesse ls were constricted straight, the branches decreased, and alarge nonperfusion area was observed at the 12th day; the large vessels were dilated and tortuous and neovascularization occurred at the 15th day; a mass of neovascularization was found and the vascular net structure of the deep and shallow layer was destroye d at the 17th day. The expression of EPO mRNA decreased from the 7th day and kee p decreasing in the whole oxygen-breathing duration in the experimental group. A fter the mice were returned to room air, the expression increased obviously from the 15th day and kept the high level until the 21st day. The expression of EPO mRNA increased at the 7th day and reached the peak at the 11th day, and kept the high level until the 21st day. The changes of protein levels of these three fac tors were later than that of their mRNA, but had the same trend. The difference of the expression between the two groups at the different time point was signifi cant except for the 7thday point (Plt;0.05). Conclusion It 's suggested that EPO and EPOR played important roles on the development of normal retina vascularizati on and the pathogenesis of ROP, which may provide new conception and method for the prevention and treatment of the oxygen-induced retinopathy.
Objective To determine the effect of methimazole (MMI) on retinal vascular development in neonatal rats, and to investigate the relationship between the concentration of insulin-like growth factor-I (IGF-I) in serum and the development of normal blood vessels and between the concentration of IGF-I and the formation of abnormal blood vessels. Methods There were 75 neonatal SpragueDawley rats in experimental group whose mothers were raised with water with 0.1% MMI at the first day of parturition. Another 50 neonatal rats were in the control group whose mothers were raised with normal water. The rats in the two groups were sub-divided into 4day and 10day subgroup, respectively. The retinal flatmount of the right eyes were stained with adenosine diphosphatase (ADPase); with the paraffin section of the left eyes, the number of nucleolus breaking through retinal inner limiting membrane was counted and the retinal blood vessels were evaluated. Serum IGF-I levels were detected by radioimmunoassay, and the weight of the neonatal rats in each group were observed and recorded. Results The incidence of retinal neovascularization in 10 day MMI group was 27%, and 0% in 4-day MMI group and control group. The serum IGF-I level in 4-day and 10-day MMI group (73.07 ng/ml, 175.13 ng/ml) was obviously lower than which in the 4-day and 10-day control group (168.73 ng/ml,306.38 ng/ml) （P=0.00）. Obvious slow growth of the neonatal rats was found in MMI group compared with which in the control group. Conculsions MMI may inhibit the normal growth of retinal blood vessels and lead neovascularization, which may relate to the initial decrease of the serum IGF-I level. (Chin J Ocul Fundus Dis, 2007, 23: 198-201)
ObjectiveTo detect the development of retinal neovascularization (NV) induced by metabolic acidosis in neonatal rats and investigate the relationship between the occurrence of NV and vascular endothelial growth factor (VEGF). MethodsA total of 425 newborn Sprague-Dawley rats in experimental group underwent tubal feeding of NH4Cl (535 mg/kg) with the concentration of (50 mg/ml) (twice per day) from the 2nd day after the birth for 6 days and followed by a period of recovery. Additional 150 neonatal rats were in the control group without the tubal feeding. The rats were executed at the 3rd, 5th, 8th, 10th, 13th, 20th day after birth respectively. The retinal vessels were evaluated through retinal stretched preparation andadenosine diphosphatase (ADPase) staining; VEGF in retina was detected by enzymelinked immunosorbent assay(ELISA).ResultsIn the experimental group, the incidence of retinal NV at the 3rd, 5th, 8th, 10th, 13th, 20th day after birth was 0%，9%，26%，55%，19%, and 0% respectively. At the 3rd day, the expression of VEGF protein was lower in experimental group ［（101.1±14.2 ）pg/mg］ than that in the control group ［（133.2±15.9） pg/mg］（P＝0.004）, while at the 8th day it was higher in experimental group［(98.4±19.2) pg/mg］than that in the control group［（78.1±8.7） pg/mg］（P=0.028). There was no significant difference between the two groups at the 5th, 10th, 13th, and 20th day (Pgt;0.05). ConclusionsMetabolic acidosis may induce NV by injuring the developing retinal vessels. Retinal NV induced by acidosis relates to VEGF. (Chin J Ocul Fundus Dis, 2005,21:296-299)
ObjectiveTo retrospectively analyze incidence and trends of retinopathy of prematurity (ROP) from 2004 to 2013 in Shenzhen. MethodsA total of 9100 preterm children (5401 males, 3699 females) were screened for ROP in Shenzhen from January 2004 to June 2013 using binocular ophthalmoscope or RetCam Ⅱ. First examination was performed from 4-6 weeks after birth. The birth weight was 520-2990 g with an average of (1710±410) g.The gestational age were 24-36 weeks with an average of (31.57±1.99) weeks. The gestational age of 208 children were <28 weeks, 3608 children were 28-32 weeks, 3553 children was 33-34 weeks, 1731 children was >34 weeks. The ocular findings were recorded according to the International Classification of ROP and The Early Treatment for ROP. Only the more aggressive eye of bilateral asymmetrical cases was counted for statistical purpose, and the cases required surgeries were defined as severe cases. The 10 years period was divided into first phase (2004-2008) and second phase (2009-2013). The incidence of ROP and severe ROP of these two phases was compared and statistics was analyzed. ResultsIn the past 10 years, the overall incidence of ROP and sever ROP in Shenzhen was 12.49% and 4.99% in this screen. The children were divided into 4 groups according to the birth weight, the ROP incidences of birth weight <1000 g, 1000-1499 g, 1500-1999 g and ≥2000 g were 62.62%, 28.40%, 11.34% and 3.63% respectively. The severe ROP incidences were 34.95%, 12.21%, 3.73% and 0.49% respectively in these birth weight groups. The children were divided into 4 groups according to gestational weeks, the ROP incidences of gestational age <28 weeks, 28-32 weeks, 33-34 weeks and >34 weeks were 67.31%, 25.27%, 7.22% and 3.87% respectively. Severe ROP incidences were 37.02%, 10.71%, 1.79% and 0.68% in these gestational age groups respectively. ROP and severe ROP incidences were decreased from 14.64% at first phase to 11.47% at second phase, and from 6.52% at first phase to 4.26% second phase respectively, the differences were statistical significant (χ2=26.96, 26.61; P<0.05). ROP and severe ROP incidence in <1000 g birth weight group at second phase were much less than the first phase (χ2=13.676, 5.271; P<0.05). In <28 weeks gestational age group, the ROP incidence was the same in first phase and second phase (χ2=0.843, P>0.05), but the severe ROP incidence at second phase was much less the first phase (χ2=4.757,P<0.05). ConclusionFrom 2004 to 2013, the incidences of ROP and severe ROP have decreased significantly in Shenzhen.
ObjectiveTo observe the expression of CD147, matrix metalloproteinases-2 (MMP-2) and vascular endothelial growth factor (VEGF) in a rat model of oxygen induced retinopathy (OIR). MethodsEighty-four neonatal Wistar rats were divided into two groups randomly, the hyperoxia group (n=42) and the control group (n=42). Oxygen induced retinopathy was established in the hyperoxia group, the control group was raised in room air. Wholemonts were prepared from postnatal day (p) 7 and 14 rat retina to observe retinal vascular morphology. The number of endothelial cells to break through the internal limiting membrane was counted from p14 retinal paraffin sections. Expression of CD147, MMP-2 and VEGF protein levels was analyzed by immunohistochemistry on p12, p14, and p16 retinal sections. At the meantime, correlation between CD147 and MMP-2, VEGF was analyzed by two-way analysis of variance (ANOVA) test. ResultsAt p7, the retinal vasculature of the control group was radial distributed with large caliber. In OIR group, there were vasoconstriction, large area of avascular zone and a few small areas of vascular network. At p14, the normal untreated rat had interwoven retinal vasculature, but in OIR group, the retinal vasculature was expanded and tortuous, and forming lots of neovascular cluster in the boundary of the perfusion and non-perfusion regions resulting exudation and hemorrhage. At p14, the endothelial cell nuclei breakthrough the internal limiting membrane was (1.30±1.26) and (19.70±3.56) respectively in control and OIR group, the difference was statistically significant (t=21.813, P<0.01). Immunohistochemical staining showed that CD147, MMP-2, VEGF expression was low in control group but high in OIR group. From p12 to p16, CD147, MMP-2 and VEGF protein expression increased in OIR retinas compared with control samples(p12:t=5.612, 4.122, 4.955; P<0.01. p14:t=11.390, 8.047, 12.176; P<0.01. p16:t=6.355, 4.422, 5.110; P<0.01). ConclusionCD147, MMP-2 and VEGF were highly expressed in the rat model of oxygen induced retinopathy.
The exact pathophysiological mechanisms of retinopathy of prematurity (ROP) remain elusive. The risk factors of ROP include excessive oxygen therapy, malnutrition, infection and inflammation. Among the factors above, the effect of inflammation on ROP has received more attention. TNF-α is a biological active protein which is involved in neovascularization and inflammation. It may play a role in the development of ROP. This review summarized the studies on the association between TNF-α and ROP in recent years, so as to provide a new way to further study the pathogenesis and treatment methods of ROP.