ABSTRACT
Morphology of the absorber plays a decisive role in photoelectric conversion efficiency (PCE) of kersterite solar cells. Cu2ZnSn(S,Se)4 (CZTSSe) grain prepared from dimethyl sulfoxide (DMSO)-based solution easily grows into large grains, which can lead to the formation of some holes at the back of the absorber. These holes cause the recombination of photocarriers and greatly weaken the performance of CZTSSe devices. Here, trace amounts of thioglycolic acid (TGA) are introduced to the DMSO-based solution, and a combination of TGA and metal is formed in the absorber, leading to the formation of fine grains in the CZTSSe absorber. Next, post-annealing (PA) in a N2 atmosphere is performed to promote Na diffusion, helping the transition from a fine-grain layer to a low-resistivity carbon layer at the interface between CZTSSe and Mo and avoiding the drawbacks of the DMSO-based system. Finally, the champion PCE of the CZTSSe device can be improved to 10.05% from 8.06%. The conclusions demonstrate that the construction of a carbon layer can boost the performance of CZTSSe devices.
ABSTRACT
PURPOSE: To test the hypothesis that early in the course of diabetes, apparent ion demand within the retina is impaired and may be corrected by alpha-lipoic acid (LPA), a drug that inhibits vascular histopathology. METHODS: Intraretinal manganese ion uptake and retinal thickness were measured from high-resolution manganese-enhanced MRI (MEMRI) data of control and streptozocin diabetic male Sprague-Dawley (SD) rats and of control and diabetic female Lewis rats with and without treatment with LPA. In a subgroup of male SD rats, blood-retinal barrier (BRB) integrity was also assessed with dynamic contrast-enhanced MRI. In addition, ion-coupled plasma-mass spectrometry (ICP-MS) was used to measure baseline whole manganese levels from retinas of control and diabetic rats. RESULTS: Manganese ion uptake by receptor and postreceptor retina was subnormal in each untreated diabetic groups, and these deficiencies could be corrected with LPA treatment. ICP-MS studies found no differences in baseline retinal manganese concentration between control and diabetic rats. In 3-month-old diabetic male SD rats, total and postreceptor retinal thickness increased (P < 0.05) without loss of BRB integrity. In contrast, in untreated and treated diabetic female Lewis rats, retinal thicknesses were normal. CONCLUSIONS: The present results support the hypothesis that LPA can correct the impaired apparent ion demand in experimental diabetic retinopathy.
Subject(s)
Antioxidants/therapeutic use , Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/metabolism , Manganese/metabolism , Retina/metabolism , Thioctic Acid/therapeutic use , Animals , Blood-Retinal Barrier , Capillary Permeability , Diabetes Mellitus, Experimental/complications , Diabetic Retinopathy/etiology , Female , Hyperglycemia/metabolism , Magnetic Resonance Imaging , Male , Rats , Rats, Inbred Lew , Rats, Sprague-Dawley , Retina/drug effects , Retina/pathology , Spectrometry, Mass, Electrospray IonizationABSTRACT
PURPOSE: To provide proof-of-concept that the extent of intraretinal manganese uptake after systemic MnCl(2) injection, detected with manganese-enhanced MRI (MEMRI), assesses alterations in intraretinal ion demand in models of ocular insult. METHODS: In Sprague-Dawley rats, retinal ion demand and thickness were measured from MEMRI data collected before, 4 hours after, or 1, 3, and 7 days after intraperitoneal injection of MnCl(2). Choroidal contribution or blood-retinal barrier permeability surface area product (BRB PS') was determined using MRI after Gd-DTPA injection. Ocular injury was evaluated 24 hours after intravitreal injection of phosphate-buffered saline (PBS, vehicle) or PBS + ouabain, or after intraperitoneal injection of sodium iodate. Manganese retinal toxicity was assessed by comparing full-field, white-flash electroretinographic (ERG) data obtained before and after systemic MnCl(2) administration. Rat choroidal thickness was measured from cross-sections prepared from paraformaldehyde-perfused adult rats. RESULTS: Comparing pre- and post-Gd-DTPA images demonstrated minimal choroidal contribution to intraretinal analysis. Intraretinal signal intensity returned to baseline by 7 days after MnCl(2) injection. After ouabain injection, receptor and postreceptor uptake of manganese were subnormal (P < 0.05). After sodium iodate exposure, intraretinal manganese uptake was supernormal (P < 0.05) and did not increase with increasing BRB PS'. ERG data did not show any effect of MnCl(2) on photoreceptor a-wave and postreceptor b-wave relative to baseline at either observation time. CONCLUSIONS: MEMRI measurements of uptake of systemically administered and nontoxic doses of manganese appear to be a powerful approach for measuring alteration in intraretinal ion demand in models of ocular injury.
Subject(s)
Chlorides , Magnetic Resonance Imaging/methods , Manganese Compounds , Retina/pathology , Retinal Diseases/pathology , Animals , Blood-Retinal Barrier/metabolism , Chlorides/pharmacokinetics , Chlorides/toxicity , Choroid/blood supply , Contrast Media , Electroretinography , Enzyme Inhibitors/toxicity , Female , Gadolinium DTPA , Iodates/toxicity , Magnetic Resonance Imaging/standards , Manganese Compounds/pharmacokinetics , Models, Biological , Ouabain/toxicity , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Retina/physiology , Retinal Diseases/chemically induced , Retinal Diseases/physiopathologyABSTRACT
PURPOSE: To test the hypothesis that preventative alpha-lipoic acid (LPA) treatment corrects an abnormal retinal oxygenation response in experimental diabetic retinopathy. METHODS: Retinal oxygenation (DeltaPO2) was measured by MRI before (room air [ra]) and during a 4-minute carbogen inhalation challenge in five groups: control Sprague-Dawley (SD) and Lewis (LEW) rats, 3- to 4-month diabetic SD and LEW rats, and 4-month diabetic LEW rats preventatively treated with a chow LPA admix (400 mg/kg per chow). Comparisons were made between the initial 2 minutes of oxygenation change (measured using ra and first carbogen periods [t1 - ra]) and the next 2-minute change (assessed with first and second carbogen periods [t2-t1]) for superior and inferior hemiretinal DeltaPO2. RESULTS: In control SD rats, DeltaPO2(t1-ra) > DeltaPO2(t2-t1) (P <0.05) was found panretinally. In diabetic SD rats, the superior, but not the inferior, hemiretina had subnormal DeltaPO2(t1- ra) (P < 0.05) and supernormal DeltaPO2(t2-t1) (P < 0.05). In control LEW rats, DeltaPO2(t1-ra) and DeltaPO2(t2-t1) were not significantly different (P > 0.05). Also, control and diabetic LEW rat panretinal DeltaPO2(t1-ra) were lower (P < 0.05) than in the respective SD groups. In diabetic LEW rats, a supernormal (P < 0.05) panretinal DeltaPO2(t2-t1) was found that could be corrected with preventative LPA treatment. CONCLUSIONS: These data support the hypothesis and suggest that the influence of strain differences on the interpretation of retinovascular DeltaPO2 as a surrogate of drug treatment efficacy for diabetic retinopathy may be minimized by measuring a late-phase supernormal response. The LPA data raise the possibility that oxidative stress contributes to diabetes-induced supernormal DeltaPO2.
Subject(s)
Antioxidants/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetic Retinopathy/drug therapy , Oxygen Consumption , Oxygen/metabolism , Retina/drug effects , Thioctic Acid/therapeutic use , Animals , Carbon Dioxide/administration & dosage , Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/metabolism , Hyperoxia/metabolism , Magnetic Resonance Imaging , Oxidative Stress , Oxygen/administration & dosage , Partial Pressure , Rats , Rats, Inbred Lew , Rats, Sprague-Dawley , Retina/metabolismABSTRACT
PURPOSE: To test the hypothesis that bosentan (a dual ET(A)/ET(B) receptor antagonist) corrects a subnormal retinal oxygenation response in the STZ-induced diabetic rat. METHODS: In benchtop experiments, ET-1 was acutely injected into the vitreous of control and 5- to 7-day bosentan-treated nondiabetic rats. Major retinal vessel diameters were analyzed from ADPase-stained flatmounts. Retinal oxygenation (DeltaPo(2)), an established early surrogate marker of drug treatment efficacy, was measured by MRI during a 2-minute carbogen inhalation challenge in four groups: control rats (n = 7), control rats treated with bosentan (n = 7), 3-month diabetic rats (n = 9), and 3-month diabetic rats treated with bosentan (n = 5). Effect of baseline differences was studied in control rats breathing either room air (n = 5) or 12% oxygen breathing (n = 5) before a 2-minute carbogen provocation. RESULTS: ET-1 produced a significant (P < 0.05) reduction in retinal arterial diameter that was suppressed (P > 0.05) in rats fed bosentan chow admix. For all groups, no MRI baseline signal intensity differences were found (P > 0.05). Also, comparisons between baseline room air and 12% conditions and control rats fed normal chow or a bosentan admix both produced similar (P > 0.05) panretinal DeltaPo(2). In treated and untreated diabetes groups, inferior hemiretinal DeltaPo(2) remained normal (P > 0.05), but superior hemiretinal DeltaPo(2) was subnormal (P < 0.05). CONCLUSIONS: Because subnormal retinal DeltaPo(2) after drug treatment is a biomarker of subsequent vascular histopathology, the present data raise the possibility that retinal ET-1 does not play a key role in the pathogenesis of diabetic retinopathy.
Subject(s)
Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/metabolism , Endothelin A Receptor Antagonists , Endothelin B Receptor Antagonists , Oxygen/metabolism , Retina/metabolism , Animals , Apyrase/metabolism , Bosentan , Endothelin-1/pharmacology , Magnetic Resonance Imaging , Oxygen Consumption , Partial Pressure , Rats , Retinal Vessels/drug effects , Retinal Vessels/enzymology , Retinal Vessels/pathology , Sulfonamides/administration & dosageABSTRACT
PURPOSE: To test the hypothesis that high-resolution (23.4 microm intraretinal resolution) manganese-enhanced magnetic resonance imaging (MEMRI) can be used to noninvasively and simultaneously record from distinct layers of the rat retina cellular demand for ions associated with functional adaptation. METHODS: In control rats, high-resolution images were collected with or without systemic injection of MnCl2 during light or dark adaptation; inner and outer retinal signal intensities were compared. In separate experiments, 1 month after systemic administration of MnCl2 to awake dark-adapted control rats, possible toxic effects of Mn2+ on ocular health were assessed with the use of the following metrics: retinal layer thickness, intraocular pressure, and blood retinal barrier integrity. RESULT: In nonmanganese-injected rats, the signal intensity difference between light and dark states for inner and outer retina was not significantly different (P>0.05). In contrast, after manganese administration, the change in outer retinal signal intensity under light/dark conditions was significantly greater than that of inner retina. At 1 month after MnCl2 injection, comparisons with controls revealed no evidence for deleterious ocular health effects as assessed by whole and inner retinal thickness, intraocular pressure, and blood retinal barrier integrity. CONCLUSIONS: The present MEMRI examination was a safe (i.e., nontoxic) and relatively straightforward procedure that appeared to robustly reflect layer-specific retinal ion demand that correlates with normal retinal physiology responses associated with light and dark visual processing. Comprehensive MEMRI measures of retinal ion demand may be envisioned in a range of animal models for the study of normal development and aging.
Subject(s)
Chlorides , Magnetic Resonance Imaging/methods , Manganese Compounds , Retina/physiology , Animals , Blood-Retinal Barrier/physiology , Chlorides/toxicity , Dark Adaptation/physiology , Intraocular Pressure/drug effects , Light , Oxygen/metabolism , Oxygen Consumption , Rats , Rats, Sprague-Dawley , Retina/drug effectsABSTRACT
PURPOSE: To test the hypothesis that subnormal retinal oxygenation response (DeltaPo2) found at 3 months of experimental diabetes is associated with cellular swelling and increased retinal thickness. METHODS: Two groups of animals were studied: control rats injected intraperitoneally with either 15% body weight of saline or distilled water (cellular swelling model) or with intravitreal N-methyl-D-aspartate (NMDA) and 3-month-old diabetic and age-matched control rats. Intraocular pressure and retinal thickness was assessed using an applanation tonometer or high-resolution MRI (23.4 microm2 in-plane). In separate studies, functional MRI was used to measure blood-retinal barrier (BRB) integrity after Gd-DTPA injection intravenously and retinal DeltaPo2 during carbogen provocation. RESULTS: Inner and total retinal thickness were lower (P < 0.05) after NMDA injection, not different (P > 0.05) between control, before and after saline injection and before distilled water injection, and supernormal (P < 0.05) after distilled water injection. In diabetic rats, thickness was normal (P > 0.05) at most distances from the optic nerve but was subnormal (P < 0.05) in superior retina (0.5 mm from the optic nerve). Intraocular pressure was not different (P > 0.05) between groups. BRB was intact (P > 0.05) after saline and distilled water injection. DeltaPo2 was normal (P > 0.05) after saline injection and over inferior hemiretina of the diabetic group but was subnormal (P < 0.05) after distilled water injection and over superior hemiretina of diabetic rats. CONCLUSIONS: The lack of increased thickness in 3-month-old diabetic rats in vivo raises the possibility that intracellular swelling is unlikely to underlie subnormal DeltaPo2 in experimental diabetes. In diabetic rats, the spatial disconnect between subnormal DeltaPo2 pansuperiorly and retinal thinning only superiorly to the optic nerve suggests that neurovascular coupling is perturbed.
Subject(s)
Diabetic Retinopathy/pathology , Oxygen Consumption , Retina/pathology , Animals , Blood-Retinal Barrier , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Retinopathy/metabolism , Excitatory Amino Acid Agonists/administration & dosage , Intraocular Pressure , Macular Edema/chemically induced , Macular Edema/pathology , Magnetic Resonance Imaging , N-Methylaspartate/administration & dosage , Oxygen/metabolism , Partial Pressure , Rats , Rats, Sprague-Dawley , Retina/drug effects , Tonometry, Ocular , Water/administration & dosageABSTRACT
PURPOSE: Early subnormal retinal oxygenation response to a hyperoxic provocation (DeltaPo2) is strongly associated with subsequent experimental diabetic retinopathy and can be reversed by drug treatments started with the induction of diabetes. It is not yet known whether drug treatment can reverse an established subnormal DeltaPo2. METHODS: Retinal DeltaPo2 was measured in two separate experimental paradigms in streptozotocin-induced diabetic rats. In a prevention study, measurements were performed in untreated diabetic rats, 3 months after the initiation of hyperglycemia (D3mo), in age-matched nondiabetic rats (C3mo), and in diabetic rats treated orally for 3 months with celecoxib, a cyclooxygenase (COX)-2-selective inhibitor, (D3mo+COX2i). In an intervention study, measurements were performed in untreated diabetic rats 4 months after the initiation of diabetes (D4mo), in age-matched nondiabetic rats (C4mo), and in diabetic rats that were untreated for 3 months and then were orally treated for an additional month with either celecoxib (D4mo+COX2i) or l-N (6)-(1-iminoethyl)lysine 5-tetrazole amide, a prodrug of an inhibitor of inducible nitric oxide synthase (iNOS, D4mo+ iNOSi). RESULTS: In the prevention arm, subnormal (P < 0.05) retinal DeltaPo2 was found in the D3mo group, but not in the D3mo+COX2i group (P > 0.05). In a previous study, it was reported that retinal DeltaPo2 also corrected in a D3mo+iNOSi group. In the intervention arm, retinal DeltaPo2 levels in the D4mo and D4mo+iNOSi, but not the D4mo+COX2i, groups were (P < 0.05) subnormal. CONCLUSIONS: These results demonstrate, for the first time, that drug treatment can reverse an established subnormal DeltaPo2. Furthermore, this effect could not be predicted by a drugs' ability to prevent the development of subnormal DeltaPo2.
Subject(s)
Cyclooxygenase Inhibitors/therapeutic use , Diabetes Mellitus, Experimental/prevention & control , Diabetic Retinopathy/prevention & control , Nitric Oxide Synthase/antagonists & inhibitors , Oxygen Consumption/drug effects , Retina/drug effects , Animals , Blood Glucose/metabolism , Carbon Dioxide/administration & dosage , Celecoxib , Diabetes Mellitus, Experimental/physiopathology , Diabetic Retinopathy/physiopathology , Enzyme Inhibitors/therapeutic use , Lysine/analogs & derivatives , Lysine/therapeutic use , Magnetic Resonance Imaging , Nitric Oxide Synthase Type II , Oxygen/administration & dosage , Oxygen/metabolism , Oxygen Consumption/physiology , Partial Pressure , Pyrazoles/therapeutic use , Rats , Retina/physiopathology , Sulfonamides/therapeutic useABSTRACT
PURPOSE: To test the hypothesis that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a useful in vivo measure of passive blood retinal barrier permeability surface area product (BRB PS) in experimental diabetic retinopathy. METHODS: BRB PS (cm(3)/min) was measured using DCE-MRI and Gd-DTPA (MW 590 Da) in urethane-anesthetized control rats, sodium iodate-treated rats, rats receiving intravitreally injected human serum albumin (HSA) or vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), or in rats that were diabetic for 2, 4, 6, or 8 months. RESULTS: Sodium iodate-treated rats exhibited an eightfold increase (P < 0.05) in BRB PS compared to that in control animals. Furthermore, in iodate-treated rats, the average vitreous signal enhancement was linearly dependent on Gd-DTPA dose (r = 0.91, P < 0.0001). Six hours postinjection, VEGF/VPF-treated rats exhibited a threefold increase in BRB PS (P < 0.05) compared to eyes injected with HSA. In 2-, 4-, and 6-month diabetic rats, BRB PS was not significantly different (P > 0.05) from control BRB PS values. After 8 months of diabetes, a twofold increase (P < 0.05) in PS over control PS values was found. DCE-MRI demonstrated that the BRB becomes leaky immediately before death, possibly causing an artificial increase in retinal permeability in methods that require enucleation or retinal isolation to assess permeability. CONCLUSIONS: DCE-MRI provides a sensitive, noninvasive, and linear assay that accurately measures, without potential artifacts associated with death and enucleation, passive BRB PS in experimental diabetes. DCE-MRI BRB PS measurements are expected to provide a useful surrogate marker of drug treatment efficacy.
Subject(s)
Blood-Retinal Barrier , Diabetes Mellitus, Experimental/diagnosis , Diabetic Retinopathy/diagnosis , Magnetic Resonance Imaging , Retinal Vessels/pathology , Animals , Capillary Permeability/drug effects , Contrast Media , Gadolinium DTPA , Iodates/pharmacology , Rats , Serum Albumin/pharmacology , Vascular Endothelial Growth Factor A/pharmacologyABSTRACT
PURPOSE: To determine the effect of methylimidazole (MMI)-induced hypothyroidism in a newborn rat model of low retinal neovascular (NV) incidence. METHODS: Control and MMI-exposed newborn rats were raised either in room air or variable oxygen (40/15) until P14. All groups were then exposed to room air between postnatal day (P)14 and P20. Dams drank either tap water or water containing MMI. Eyes of animals in all groups were enucleated, and retinas were removed and stained with adenosine diphosphatase and analyzed for peripheral avascularity, vascular density, and NV incidence and severity. RESULTS: In the control group, MMI treatment did not promote the development of retinal NV although a linear relationship (r = 0.99, P < 0.01) was found between increased MMI dose and lower peripheral retinal vascular densities. In all the 40/15 groups, peripheral retinal vascular densities were lower (P < 0.05) than normal and were not a function of MMI dose. Increased MMI dose produced increased retinal incidence of NV (r = 0.99, P < 0.05). CONCLUSIONS: These data are consistent with the notions that thyroid function contributes to normal retinal vascular density and that hypothyroidism can play a permissive role in the development of retinal NV.
Subject(s)
Disease Models, Animal , Hypothyroidism/physiopathology , Retinal Neovascularization/physiopathology , Adenosine Diphosphate/metabolism , Animals , Animals, Newborn , Antithyroid Agents/toxicity , Hyperoxia/physiopathology , Hypothyroidism/chemically induced , Incidence , Methimazole/toxicity , Oxygen/administration & dosage , Rats , Rats, Sprague-Dawley , Retinal Vessels/pathology , Thyroid Gland/physiologyABSTRACT
PURPOSE: To test the hypotheses that, in mice, breathing carbogen (95% O(2)-5% CO(2)) oxygenates the retina better than breathing 100% oxygen, the superior hemiretinal oxygenation response to carbogen inhalation is subnormal early in diabetes, and diabetes-induced elevation of retinal protein kinase C (PKC)-beta contributes to this pathophysiology. METHODS: Retinal oxygenation response (DeltaPO(2)) was measured using functional magnetic resonance imaging (MRI) and either carbogen or 100% oxygen inhalation challenge in C57BL/6J control (C) mice. Retinal DeltaPO(2) during carbogen breathing was also measured in PKCbeta knockout (C57BL6-Prkcb1; [KO]), 4 month C57BL/6J diabetic (D), and 4-month diabetic PKCbeta KO (D+KO) mice. Retinal PKCbeta protein expression was assessed by Western analysis. RESULTS: In C mice, retinal DeltaPO(2) during carbogen breathing was significantly greater (P < 0.05) than during oxygen breathing. In D mice, DeltaPO(2) during carbogen breathing was significantly lower than normal in the superior, but not the inferior, hemiretina and was normal (P > 0.0 5) in the KO group. In the D+KO mice DeltaPO(2) was normal (P > 0.05) only at distances less than 1.5 mm from the optic nerve head. PKCbeta expression was elevated in the retina in diabetes (P < 0.05), but was significantly decreased (P < 0.05) in D+KO mice. CONCLUSIONS: The present study confirms that, in the mouse, retinal DeltaPO(2) patterns during different inhalation challenges or in the presence of diabetes are similar to what has been reported in rats. Diabetes-induced elevation of PKC appears to contribute only focally to subnormal retinal DeltaPO(2). This raises the possibility that PKC inhibition therapy may be only regionally effective in treating retinal pathophysiology associated with diabetic retinopathy.
Subject(s)
Diabetes Mellitus, Experimental/metabolism , Oxygen Consumption/physiology , Protein Kinase C/metabolism , Retina/physiology , Administration, Inhalation , Animals , Blotting, Western , Carbon Dioxide/administration & dosage , Diabetic Retinopathy/metabolism , Disease Models, Animal , Isoenzymes/genetics , Isoenzymes/metabolism , Magnetic Resonance Imaging , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxygen/administration & dosage , Protein Kinase C/genetics , Protein Kinase C beta , Retina/enzymologyABSTRACT
We aimed to test the hypothesis that the inducible form of nitric oxide synthase (iNOS) contributes to the development of an early subnormal retinal oxygenation response in preclinical models of diabetic retinopathy. In urethane anesthetized Sprague Dawley rats or C57BL/6 mice, functional magnetic resonance imaging was used to noninvasively measure the change in retinal oxygen tension (Delta PO(2)) during a carbogen-inhalation challenge. In the rat experiments, the retinal Delta PO(2) of the following groups were compared: control rats (n = 9), 3-month diabetic rats (n = 5), and 3-month diabetic rats treated orally with L-N(6)-(1-iminoethyl)lysine 5-tetrazole amide, a prodrug of an inhibitor of iNOS (n = 6). In addition, the retinal Delta PO(2) of the following mouse groups were compared: C57BL/6 mice (n = 20), C57BL/6-Nos2(tm1 Lau) mice (n = 10), 4-month diabetic mice (n = 13), and 4-month diabetic knockout mice (n = 6). Only the Delta PO(2) of the superior hemiretina of the diabetic rat and mice groups were significantly subnormal (P < 0.05). The superior Delta PO(2) of the diabetic rats treated with the prodrug was not significantly (P > 0.05) different from their respective normal controls. In the mice experiments, the superior retinal Delta PO(2) of the iNOS null mice was not statistically different (P > 0.05) from that of normal control mice. iNOS is required for the development of an early subnormal Delta PO(2) in experimental diabetic retinopathy.
Subject(s)
Diabetic Retinopathy/physiopathology , Oxygen Consumption/physiology , Retina/physiopathology , Animals , Blood Glucose/metabolism , Carbon Dioxide/blood , Diabetic Retinopathy/diagnosis , Disease Models, Animal , Hydrogen-Ion Concentration , Magnetic Resonance Imaging , Mice , Nitric Oxide/metabolism , Optic Nerve/physiopathology , Oxygen/blood , Partial Pressure , RatsABSTRACT
PURPOSE: To test the hypothesis that in an experimental model of retinopathy of prematurity (ROP) rat pups that are at risk for but do not have retinal neovascularization (NV) exhibit a normal oxygenation response to a hyperoxic inhalation challenge. METHODS: Newborn Sprague-Dawley rats were raised under two varied oxygen conditions (50/10 or 40/15, indicating percent of oxygen in the air on alternate days) for 14 days and then allowed to recover in room air. Functional magnetic resonance imaging was used to determine the retinal oxygenation response (increase in partial oxygen pressure in the vitreous over the room air value, or deltaPO(2), in mm Hg) to hyperoxic inhalation challenge. Adenosine diphosphatase (ADPase)-stained retinas were analyzed to determine the NV incidence and severity. RESULTS: On postnatal day (P)20, the 40/15 procedure produced significantly (P < 0.05) lower incidence of NV than the 50/10 protocol (8% vs. 99%, respectively). Retinal deltaPO(2) during carbogen breathing of the 40/15 animals that did not have evidence of NV was not different (P > 0.05) from that of normal age-matched animals; later time points were not examined. At P26 and P34, in 50/10 rats that no longer had NV, retinal deltaPO(2)s during carbogen breathing were significantly (P < 0.05) lower than that of age-matched control pups. At P34 in control rats, but not in 50/10 rats, deltaPO(2) was 61% greater (P < 0.05) during carbogen breathing than during oxygen breathing. CONCLUSIONS: The results from 40/15 experiments, together with the authors' previous data in 50/10 rats, which documented subnormal retinal deltaPO(2) before and during NV, provides additional support that subnormal retinal oxygenation to an inhalation challenge is an important event associated with the development of NV. In addition, 50/10 rats that no longer demonstrated NV had a persistent subnormal retinal deltaPO(2), suggesting a continuing risk of development of additional retinal complications after resolution of the NV in ROP.