Novel elucidation and treatment of pancreatic chronic graft-versus-host disease in mice

Chronic graft-versus-host disease (cGVHD) is a severe complication of allogeneic haematopoietic stem cell transplantation. There is a growing understanding of cGVHD, and several effective therapies for cGVHD have been reported. However, pancreatic cGVHD is a potentially untapped study field. Our thought-provoking study using a mouse model of cGVHD suggested that the pancreas could be impaired by cGVHD-induced inflammation and fibrosis and that endoplasmic reticulum (ER) stress was augmented in the pancreas affected by cGVHD. These findings urged us to treat pancreatic cGVHD through reduction of ER stress, and we used 4-phenylbutyric acid (PBA) as an ER stress reducer. A series of experiments have indicated that PBA can suppress cGVHD-elicited ER stress in the pancreas and accordingly alleviate pancreatic cGVHD. Furthermore, we focused on a correlation between epithelial to mesenchymal transition (EMT) and fibrosis in the cGVHD-affected pancreas, because EMT was conceivably implicated in various fibrosis-associated diseases. Our investigation has suggested that the expression of EMT markers was increased in the cGVHD-disordered pancreas and that it could be reduced by PBA. Taken together, we have provided a clue to elucidate the pathogenic process of pancreatic cGVHD and created a potentially effective treatment of this disease using the ER stress alleviator PBA

Serum free fatty acids levels not associated with normal tension glaucoma

Kenya Yuki, Itaru Kimura, Kazuo TsubotaDepartment of Ophthalmology, Keio University School of Medicine, Tokyo, JapanPurpose: 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.Keywords: free fatty acid, docosahexaenoic acid, eicosapentaenoic acid, normal tension glaucom

Combination of violet light irradiation and collagenase treatments in a rabbit model of keratoconus

PurposeWe evaluated the use of collagenase treatment to generate a rabbit model of keratoconus and the impact of violet light (VL) irradiation on the disease model in six Japanese White rabbits.MethodsAfter epithelial debridement, the collagenase group was treated with a collagenase type II solution for 30 min; the control group was treated with a solution without collagenase. Three rabbits also underwent VL irradiation (375 nm, irradiance 310 μW/cm2) for 3 h daily for 7 days after topical collagenase application. Slit-lamp microscopy results, steep keratometry (Ks), corneal astigmatism, central corneal thickness, and axial length were examined before and after the procedure. The corneas were obtained on day 7 for biomechanical evaluation.ResultsA significant increase in Ks and corneal astigmatism was observed in the collagenase and VL irradiation groups compared with the control group on day 7. No significant difference was found in the change in corneal thickness between the groups. The elastic modulus at 3, 5, and 10% strain was significantly lower in the collagenase group than in the control group. There was no significant difference in the elastic modulus at any level of strain between the collagenase and VL irradiation groups. The average axial length at day 7 was significantly longer in the collagenase and VL irradiation groups than in the control group. Collagenase treatment induced a model of keratoconus by steepening the keratometric and astigmatic values. There was no significant difference in the observed elastic behavior of normal and ectatic corneas under physiologically relevant stress levels.ConclusionVL irradiation did not cause regression of corneal steepening in a collagenase-induced model during short-term observation

Correlation between contrast sensitivity and higher-order aberration based on pupil diameter after cataract surgery

Takefumi Yamaguchi1,2, Kazuno Negishi1, Kazuhiko Ohnuma3, Kazuo Tsubota11Department of Ophthalmology, Keio University School of Medicine, Tokyo; 2Department of Ophthalmology, Ichikawa General Hospital, Tokyo Dental College, Chiba; 3Department of Medical System Engineering, Faculty of Engineering, Chiba University, Chiba, JapanBackground: The purpose of this study was to evaluate the correlation between contrast sensitivity and calculated higher-order aberrations based on individual natural pupil diameter after cataract surgery.Methods: This prospective study included 120 eyes from 92 patients who were randomized to receive one of four lenses, including three aspheric lenses (Acrysof SN60WF, Tecnis ZA9000, and Hoya Py60AD) and one spherical lens (Acrysof SN60AT). Contrast sensitivity, higher-order aberrations of the whole eye, and pupil diameter under photopic and mesopic conditions were measured 1 month postoperatively. Higher-order aberrations were decomposed into Zernike coefficients, calculated according to individual pupil diameter. The correlation between higher-order aberrations and contrast sensitivity was evaluated.Results: There were no significant differences in contrast sensitivity function between the four types of lenses under photopic conditions. However, the contrast sensitivity function and area under log contrast sensitivity function in the aspheric lenses were significantly better than in the spherical lens under mesopic conditions. Under mesopic conditions, spherical aberration in eyes with aspheric lenses was significantly lower than in eyes with spherical lenses (P < 0.05). Under photopic conditions, coma aberration had a significant negative correlation with contrast sensitivity at 12 cycles/degree. Under mesopic conditions, spherical aberration had a significant negative correlation with contrast sensitivity at 3, 6, and 12 cycles/degree with glare, and with contrast sensitivity at 6 and 18 cycles/degree without glare.Conclusion: In terms of influence on visual function, coma aberration may be more significant under photopic conditions and spherical aberration under mesopic conditions.Keywords: mesopic conditions, spherical aberration, wavefront, photopic and mesopic condition

Renin-Angiotensin System Hyperactivation Can Induce Inflammation and Retinal Neural Dysfunction

The renin-angiotensin system (RAS) is a hormone system that has been classically known as a blood pressure regulator but is becoming well recognized as a proinflammatory mediator. In many diverse tissues, RAS pathway elements are also produced intrinsically, making it possible for tissues to respond more dynamically to systemic or local cues. While RAS is important for controlling normal inflammatory responses, hyperactivation of the pathway can cause neural dysfunction by inducing accelerated degradation of some neuronal proteins such as synaptophysin and by activating pathological glial responses. Chronic inflammation and oxidative stress are risk factors for high incidence vision-threatening diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. In fact, increasing evidence suggests that RAS inhibition may actually prevent progression of various ocular diseases including uveitis, DR, AMD, and glaucoma. Therefore, RAS inhibition may be a promising therapeutic approach to fine-tune inflammatory responses and to prevent or treat certain ocular and neurodegenerative diseases

Selenoprotein P Controls Oxidative Stress in Cornea

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