Published papers

PURPOSE. To investigate the applicability of in vivo laser scanning confocal microscopy in the diagnosis and follow-up of ocular demodicosis infestation in a prospective controlled study. METHODS. Fifteen right eyes of 15 patients with blepharitis associated with cylindrical dandruff (10 males, 5 females; mean age: 62.9 ± 9 years) and eight right eyes of eight age- and sex-matched control subjects underwent HRTII/RCM, evaluation of ocular symptom scores, tear function tests including vital stainings, Schirmer test, and tear clearance test, and evaluation of mite numbers in the eyelids. RESULTS. In vivo confocal microscopy effectively disclosed the mites in the terminal bulbs of the eyelashes, which were not observed after treatment. Eyelids with demodicosis infestation showed marked inflammatory infiltrates around the meibomian glands and conjunctiva, which cleared with tea tree oil treatment. CONCLUSIONS. Laser scanning confocal microscopy seems to be an efficient noninvasive tool in the diagnosis and follow-up of ocular demodicosis infestation. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Purpose of review: Recently, functional visual acuity (FVA) measurement has been reported to be an important method of determining 'masked impairment of visual function' and assessing visual acuity in detail. This review discusses a new continuous FVA measurement system for the assessment of visual performance and introduces the application of FVA measurement in cataract and intraocular lens implantation. Recent findings: The FVA was first developed to detect impaired visual function for daily activities in dry eye syndrome. The usefulness of this new methodology has been described in patients with tear instability, undergoing laser-assisted in-situ keratomileusis surgery, with Stevens-Johnson syndrome, Sjögren syndrome and mild cataract opacities. The microstructure of the lenticular opacities is highly variable (nucleus sclerosis and/or posterior capsular cataract and/or cortical opacity) causing a combination of different effects on the incident light rays that can be refracted, reflected, absorbed or scattered. In some cases, patients have a good visual acuity but may complain of disturbances in vision quality. We reported the improvement of FVA after cataract surgery in patients with mild cataracts and visual symptomatology despite a good preoperative and postoperative conventional visual acuity. To detect visual impairment due to cataract, measurement of FVA was useful in the evaluation of vision quality and changes in kinetic vision after phacoemulsification surgery. Summary: FVA measurement is an effective and noninvasive test that reflects the complaints of blurring/glare and postoperative satisfaction in patients with mild cataract. © 2010 Wolters Kluwer Health.

Purpose: To determine whether epithelial-mesenchymal transition is involved in the development of corneal subepithelial fibrosis (pannus). Methods: Frozen samples of pannus tissue removed from human corneas with a diagnosis of total limbal stem cell deficiency were characterized by immunostaining for both epithelial and mesenchymal markers. We selected transformation-related protein 63 (p63) and pancytokeratin as epithelial markers and vimentin and α-smooth muscle actin (α-SMA) as mesenchymal markers. Immunostaining for β-catenin and E-cadherin was performed to determine wingless- Int (Wnt)-pathway activation. RT-PCR analysis was also performed on epithelial tissue obtained from pannus samples after dispase digestion. Results: Immunohistochemistry revealed strong nuclear expression of p63 and weak intercellular expression of E-cadherin in epithelial basal cells of pannus tissue. Furthermore, translocation of β-catenin from intercellular junctions to the nucleus and cytoplasm was also observed. Double-positive cells for both p63 and α-SMA were observed in the subepithelial stroma of pannus tissue, which was supported by RT-PCR and cytospin analysis. Conclusions: Epithelial-mesenchymal transition may be partially involved in the development of subepithelial corneal fibrosis due to total limbal stem cell deficiency. © 2010 Molecular Vision.

Purpose: To evaluate the applicability of in vivo laser scanning confocal microscopy as a tool of conjunctival cytology in a prospective case-control study. Methods: Nineteen right eyes of 19 Sjogren's syndrome dry eye patients (19 females; mean age: 55.8±15 years), and 18 right eyes of 18 normal healthy control subjects (12 females and 6 males; mean age: 50.8±14 years) were evaluated in this study. The eyes were analyzed by the Heidelberg retina tomography (HRTII)/Rostock cornea module (RCM). Ocular surface and tear function tests including vital stainings (fluorescein and Rose Bengal), Schirmer test, tear film break up time (BUT), and conjunctival impression cytology were performed. After obtaining the confocal microscopy images, the mean individual epithelial cell area (MIECA), and nucleocytoplasmic (N/C) ratio were analyzed. The correlation between confocal microscopy and impression cytology parameters was also investigated. Results: The BUT, Schirmer test values, vital staining scores and squamous metaplasia grades in impression cytology were significantly worse in dry eye patients compared to controls (p<0.0001). The MIECA and the mean N/C ratios were worse in dry eye subjects compared to controls both in impression cytology and in vivo confocal microscopy (p<0.0001) with no significant differences between these parameters when the two examination techniques were compared. The MIECA and N/C ratio in conjunctival impression cytology showed significant correlation with the corresponding confocal microscopy parameters (MIECA, r2:0.557; N/C, r2:0.765). Conclusions: Laser scanning confocal microscopy seems to be an efficient non-invasive tool in the evaluation of phenotypic alterations of the conjunctival epithelium in dry eye disease. N/C ratio and MIECA appear to be two promising and new parameters of in vivo confocal cytology in the assessment of the ocular surface in dry eye disease. © 2010 Molecular Vision.

PURPOSE: To compare refractive outcomes, higher order aberrations, visual quality, and patient satisfaction between aspheric and whole-eye wavefront aspheric LASIK algorithms. METHODS: Two hundred seventy-four eyes of 152 patients undergoing LASIK for myopia and myopic astigmatism were divided into two groups: eyes that underwent treatment using either the OPD-guided customized aspheric treatment (OPDCAT) or optimized aspheric treatment zone (OATz). Both groups were subdivided into two groups based on preoperative manifest refraction spherical equivalent (MRSE) <-6.00 diopters (D) and eyes with MRSE ≥-6.00 D. Both groups were additionally subdivided into eyes with preoperative ocular higher order aberrations <0.40 μm and eyes with higher order aberrations ≥0.40 μm. A P value <.05 was considered statistically significant. RESULTS: At 3 months postoperatively, 88.3% (242/274) of eyes were available for follow-up. Postoperatively, 91.4% of eyes in the OPDCAT group and 90.6% of eyes in the OATz group were within 0.50 D. No difference in refractive outcomes and patient satisfaction among groups or subgroups was noted (P>.05). A significantly less change in asphericity (less oblate) was noted for the OPDCAT group (0.31±0.30) compared with the OATz group (0.51±0.35) (P<.05). A lower induction of aberrations in the OPDCAT group compared with the OATz group was noted (P<.05). Mesopic contrast sensitivity was significantly higher for the OPDCAT groups and subgroups (P<.05). CONCLUSIONS: Refractive outcomes between groups or subgroups were equivalent. A significantly lower induction of higher order aberrations and less change in asphericity in the OPDCAT group was noted. The OPDCAT algorithm was more likely to maintain mesopic contrast sensitivity. Copyright © SLACK Incorporated.

Purpose: A glycocalyx plays important roles in the ocular surface epithelium, but there is no direct simple method to evaluate ocular surface glycocalyx. We tested a wheat germ agglutinin conjugate of fluorescein (F-WGA) as a marker to demonstrate ocular surface glycocalyx in vivo. Methods: After a 5% F-WGA solution was applied to the eyes of eight healthy volunteers, fluorescent intensities of the central cornea and bulbar conjunctiva were measured by fluorophotometry. A 10% fluorescein-conjugated dextran solution served as the control. Changes in fluorescent intensities of the ocular surface following a challenge with 5% N-acetyl cysteine, a conventional mucolytic agent, were tested in the second experiment. Saline instillation served as a control. Results: The ocular surface was diffusely stained by F-WGA. Breakup of the precorneal tear film was not apparent, possibly because F-WGA was bound to the glycocalyx of the ocular surface epithelium. F-WGA fluorescent intensities were high in the superior, nasal, and inferior regions of the bulbar conjunctiva and low in the temporal conjunctiva and cornea. No such regional differences were observed with fluorescein-conjugated dextran. F-WGA fluorescent intensities decreased significantly with N-acetyl cysteine instillation, whereas they were not affected by saline instillation. Conclusion: The fluorophotometric method may be used to evaluate the glycocalyx quantitatively in the ocular surface in vivo. © 2010 Mochizuki et al.

Purpose: To investigate the effect of eicosapentaenoic acid (EPA) on acute ocular inflammation in an animal model of endotoxin-induced uveitis (EIU). Methods: C57Bl/6 mice (6-week-old males) were orally treated with EPA at a dose of 50 mg/kg/day for 5 days. EIU was then induced in the animals by intraperitoneal injection of 160 μg lipopolysaccharide (LPS). Twenty-four hours after LPS injection, leukocyte adhesion to the retinal vasculature was evaluated by the concanavalin A lectin perfusion-labeling technique, and leukocyte infiltration into the vitreous cavity was quantified. Furthermore, the protein levels of monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, intercellular adhesion molecule-1 and phospholyrated nuclear factor (NF)-κB p65 in the retina and retinal pigment epithelium (RPE)-choroid complex were examined by enzyme-linked immunosorbent assay (ELISA). Results: At 24 h after LPS injection, the EIU animals treated with oral EPA administration showed a significant decrease in leukocyte adhesion to the retinal vessels by 43.4% (p<0.01) and leukocyte infiltration into the vitreous cavity by 49.2% (p<0.05). In addition, EPA significantly reduced the protein levels of MCP-1 and IL-6 in the retina and the RPE-choroid complex. Furthermore, phosphorylation of NF-κB was suppressed by EPA treatment. Conclusions: Our data suggest that EPA inhibits multiple inflammatory molecules in vivo. EPA may become a novel strategy in the prevention and/or treatment of ocular inflammatory diseases. © 2010 Molecular Vision.

The ocular surface is always attacked by oxidative stress, and cornea epithelial cells are supposed to have their own recovery system against oxidative stress. Therefore we hypothesized that tears supply key molecules for preventing oxidative stress in cornea. The potential target key molecule we focused is selenoprotein P (SeP). SeP is a carrier of selenium, which is an essential trace element for many animals, for oxidative stress metabolism in the organism, and was extremely expressed in lacrimal gland. An experiment was performed with SeP eye drops in a rat dry eye model, prepared by removing the lacrimal glands. The anticipated improvement in corneal dry eye index and the suppression of oxidative stress markers were observed in SeP eye drop group. Furthermore, the concentration of SeP was significantly higher in dry eye patients compared with normal volunteers. Collectively, we concluded that tear SeP is a key molecule to protect the ocular surface cells against environmental oxidative stress. © 2010 Higuchi et al.

Purpose: Occult macular dystrophy (OMD) is a hereditary retinal disease characterized by a normal fundus, normal full-field electroretinograms (ERGs), progressive decrease of visual acuity, and abnormal focal macular ERGs. The purpose of this study was to report pattern-reversal visual-evoked potential (pVEPs) findings in OMD patients. Patients and method: The pVEPs recorded from four patients with OMD (aged 42-61 years; 2 men and 2 women) were reviewed. The visual acuities ranged from 20/200 to 20/30. The amplitudes of the N-75 and P-100 (P2 amplitude) and the latency of the N-75 components (N1 latency) were analyzed. Results: The mean (±SD) P2 amplitude was 2.7 ± 1.9 μV for the 5′, 4.8 ± 2.9 μV for the 10′, 3.2 ± 2.1 μV for the 20′, and 4.4 ± 3.5 μV for the 40′ checkerboard stimuli. The N1 latency was 122.2 ± 6.4 ms for the 5′, 105.0 ± 11.5 ms for the 10′, 97.7 ± 10.0 ms for the 20′, and 91.0 ± 13.7 ms for the 40′ checkerboard stimuli. The mean P2 amplitude was reduced and the N1 latency was delayed in comparison with the laboratory standard for the Keio University Hospital. Conclusions: The delayed latency and reduced amplitude suggest a major contribution of the central cone pathway to the pVEPs. © 2010 Hanazono et al.

Purpose: To investigate the presence of epithelial sodium channels (ENaC) in rabbit and human conjunctival epithelium and to test the effects of topical amiloride, a potassium-sparing diuretic that blocks the ENaC, on tear quantity in rabbits. Methods: Both healthy normal human and rabbit conjunctival tissues underwent immunohistochemistry staining for ENaC-α and γ subunits as well as for reverse transcription polymerase chain reaction (RT-PCR) for detection of ENaC- α and ENaC-γ subunit mRNA expression. Rabbits were instilled topical amiloride eye drops and tear function tests were performed before and after instillations. Results: Immunohistochemical staining for ENaC-α subunit in all rabbit eyes showed positive staining in apical and basal conjunctival epithelial cells. Human conjunctival epithelia revealed positive staining with ENaC-α antibody especially in the apical and basal layers. Immunohistochemistry staining with ENaC- γ antibody also revealed positive staining of the conjnunctival epithelial cells especially in the basal layers. The ENaC-α mRNA was detected in samples from healthy white rabbit conjunctival epithelia, and ENaC-α and ENaC- γ mRNAs were detected in samples from healthy human conjunctival epithelia. The mean tear quantity showed a significant increase at 15 and 30 min compared to the pre-instillation value in eyes assigned to amiloride eye drops. The mean tear quantity at 15 and 30 min was significantly higher in the amiloride group compared to the control eyes. Conclusions: Topical amiloride application appears to increase the quantity of preocular tears owing to inhibition of conjunctival epithelial sodium channels. © 2010 Molecular Vision.

Background: Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects. Methods: Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factoralpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the "Declaration of Helsinki." Results: The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores. Conclusions: The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation. © 2010 Molecular Vision.

Background: Vitamin A, B9, C, E, and uric acid are well-known antioxidants and may prevent age-related eye disorders. The aim of the present study was to investigate the levels of antioxidant vitamins, A, B9, C, E, and antioxidative substance, uric acid in the serum of Japanese patients with normal-tension glaucoma and compare the results with normal controls. Methods: All subjects with suspicion of primary open-angle glaucoma who came to the glaucoma subspeciality clinic of Keio University Hospital were enrolled in this study. Sixty patients (28 males, 32 females; mean age ± standard deviation: 59.9 ± 9.8 years) with newly diagnosed primary open-angle glaucoma patients were consecutively enrolled in this study. After the diagnosis of primary open-angle glaucoma, the patients underwent 24-h IOP measurements. Forty-seven newly diagnosed consecutive normal-tension glaucoma patients (18 males, 29 females; mean age ± standard deviation: 59.5 ± 10.2 years) were enrolled in this study. The control subjects were recruited from subjects who came to the clinic for annual refractive check-up. The 44 consecutive control subjects of the current study, (16 males, 28 females; 62.7 ± 14.8 years) did not have any ocular diseases. The serum levels of vitamins A, B9, C, E, and uric acid were measured. The values were compared between the normal-tension glaucoma and control groups by the Mann-Whitney U test. Results: Serum levels of vitamin C were significantly lower in normal-tension glaucoma patients than in normal healthy controls (P = 0.04; normal-tension glaucoma; 4.6 ± 4.0 μg/ml control; 6.3 ± 3.9 μg/ml). Uric acid level was significantly higher in normal-tension glaucoma patients than in controls (P = 0.01; normal-tension glaucoma; 5.8 ± 1.5 mg/dl control; 4.9 ± 1.4 mg/dl). No statistically significant difference was seen in vitamin A (P = 0.41; normal-tension glaucoma; 82.1 ± 26.7 μg/dl control; 77.1 ± 30.1 μg/dl), B9 (P = 0.37; normal-tension glaucoma; 8.7 ± 4.3 ng/ml control; 8.0 ± 3.1 ng/ml)and E (P = 0.83; normal-tension glaucoma; 1.5 ± 0.6 control; 1.5 ± 0.6) levels between normal-tension glaucoma and control groups. Conclusion: Normal-tension glaucoma patients had lower serum levels of vitamin C and increased levels of uric acid. These observations may pave the way for possible alternative treatment for normal-tension glaucoma. © 2009 Springer-Verlag.

Purpose: To determine the free fatty acid levels in the sera of patients with normal-tension glaucoma and compare it with that of normal controls. Methods: Forty-four consecutive patients with newly diagnosed normal-tension glaucoma and forty-four age and gender matched controls were evaluated. The type and level of fatty acids in the sera were measured by gas chromatography (Model GC17A; Shimazu, Kyoto, Japan). Twenty-four fatty acids were identified from 12:0 to 24:1. The values were compared between the normal-tension glaucoma and control groups by Mann-Whitney U tests. Results: No statistically significant difference was found in the levels of any free fatty acids between the normal-tension glaucoma group and control group. Conclusion: No significant association was found in the serum free fatty acids levels including docosahexaenoic acid and eicosapentaenoic acid between normal-tension glaucoma patients and controls. © 2010 Yuki et al, publisher and licensee Dove Medical Press Ltd.

Background: Dry eye has shown a marked increase due to visual display terminal (VDT) use. It remains unclear whether reduced blinking while focusing can have a direct deleterious impact on the lacrimal gland function. To address this issue that potentially affects the life quality, we conducted a large-scale epidemiological study of VDT users and an animal study. Methodology/Principal Findings: Cross sectional survey carried out in Japan. A total of 1025 office workers who use VDT were enrolled. The association between VDT work duration and changes in tear film status, precorneal tear stability, lipid layer status and tear secretion were analyzed. For the animal model study, the rat VDT user model, placing rats onto a balance swing in combination with exposure to an evaporative environment was used to analyze lacrimal gland function. There was no positive relationship between VDT working duration and change in tear film stability and lipid layer status. The odds ratio for decrease in Schirmer score, index of tear secretion, were significantly increased with VDT working year (P = 0.012) and time (P = 0.005). The rat VDT user model, showed chronic reduction of tear secretion and was accompanied by an impairment of the lacrimal gland function and morphology. This dysfunction was recovered when rats were moved to resting conditions without the swing. Conclusions/Significance: These data suggest that lacrimal gland hypofunction is associated with VDT use and may be a critical mechanism for VDT-associated dry eye. We believe this to be the first mechanistic link to the pathogenesis of dry eye in office workers. © 2010 Nakamura et al.

Fibrosis and excessive extracellular matrix production are characteristic features of lacrimal gland chronic GVHD (cGVHD). Tranilast (n-3,4-anthoranilic acid), used for fibrotic skin disease, inhibits transforming growth factor-Β-induced matrix production. We conducted a non-randomized study comparing 8 patients (five men, three women; median age, 47 years) given topical tranilast with 10 patients (three men, seven women; median age, 37 years) receiving therapy with topical artificial tears, sodium hyaluronate and vitamin A for mild ocular cGVHD. The tranilast group instilled topical tranilast and artificial tears q.i.d., beginning the day of dry eye diagnosis. The ocular surface and tear dynamics of each patient were evaluated before hematopoietic stem cell transplant, at the onset of dry eye and after 3 months of treatment. At 3 months, the scores of the Rose Bengal test and Schirmer test with nasal stimulation had significantly improved in the tranilast group compared with that in the control group (P<0.05). Furthermore, although five control patients (50) developed severe dry eye within the treatment period, only one tranilast-treated patient (12.5) did; the rest still had mild dry eye (P<0.05). These results suggest the hypothesis that topical tranilast may effectively retard the progression of mild dry eye associated with cGVHD. © 2010 Macmillan Publishers Limited.

Some marginal blepharitis is related to demodex, but this has not yet been reported in Japan. In this study, patients with severe marginal blepharitis with cylindrical dandruff were studied to examine the number of demodex in their cilia. Ten eyes of 10 patients (7 men and 3 women, mean age: 62.9 +/- 9.0 years) with unilateral marginal blepharitis which had cylindrical dandruff in their cilia were studied. Three cilia which had the most cylindrical dandruff were removed from the eyelids for microscopic examination. After cleaning the eyelid margins for 1 week, the examination was repeated. Scoring of itching and foreign body sensation of the patients was performed both before and after the treatment. Demodex folliculorum was detected in the cilia of 8 out of 10 eyes (80%), and 22 cilia out of 30 with cylindrical dandruff. The average number of demodex/cilia was 1.6 +/- 0.9. In all cases, the number of demodex/cillium decreased significantly with the improvement in symptoms and blepharitis. An Increase in the number of demodex might be the pathogen causing blepharitis with cylindrical dandruff, and cleaning of the eyelid margin is effective as a therapeutic method.

Purpose: To report the efficacy of simultaneous keratolimbal allograft (KLAL) surgery and deep anterior lamellar keratoplasty (DALK) for limbal stem cell deficiency (LSCD). Methods: We conducted a retrospective, interventional case series of six consecutive eyes of five patients with LSCD and stromal opacity due to gelatinous drop-like dystrophy (two eyes), Stevens-Johnson syndrome (SJS, two eyes), or aniridia (two eyes). Only patients with normal lid anatomy and Schirmer test values greater than 3 mm were enrolled. DALK was performed by viscodissection followed by a thin, 360° KLAL designed by using an artificial anterior chamber. KLAL sutures were removed after 2 weeks. Results: DALK and KLAL were successfully performed in all eyes, which were followed for an average of 17.2 ± 10.8 months. All eyes recovered a smooth corneal epithelium, although one SJS patient developed a persistent epithelial defect (PED) leading to opacification of the central cornea. Visual acuity improved by more than 2 lines in all eyes except that of the SJS patient with PED. No other complications were observed. Conclusion: Simultaneous DALK and thin-section KLAL is an effective treatment for ocular surface disease in patients with residual tear function and normal lid anatomy. © 2010 Japanese Ophthalmological Society (JOS).

PURPOSE. ABCG2 is a putative marker of progenitor cells, including the corneal epithelium. The authors investigated whether ABCG2 functions in the homeostasis of corneal epithelial cells using abcg2 knockout (KO) mice and corneal epithelial cell lines. METHODS. abcg2 KO mice and a spontaneously immortalized murine corneal epithelial cell line (TKE2) were used for experiments. Flow cytometry was used to determine the presence of side population (SP) cells based on the ability of ABCG2 to efflux Hoechst 33342 dye. Expression of ABCG2 was also examined by RT-PCR. Cytotoxicity assay (IC 50) and propidium iodide staining were performed in semiconfluent cells treated with hypoxia (1% O 2) or with the pro-oxidant mitoxantrone. RESULTS. abcg2 KO mice had a normal corneal epithelial phenotype; however, cultured abcg2 KO epithelial cells were prone to oxidative damage by mitoxantrone. TKE2 cells were resistant to mitoxantrone at low doses, but higher concentrations were toxic in a dose-dependent manner. Coculture with the ABCG2 inhibitors reserpine and Ko143 inhibited resistance to mitoxantrone, with a statistically higher cell death ratio. abcg2 KO cells were also significantly more sensitive to hypoxia than were wild-type control cells. CONCLUSIONS. ABCG2 may protect corneal epithelial progenitor SP cells against oxidative stress induced by toxins and hypoxia. © Association for Research in Vision and Ophthalmology.