Tatsuma Kishimoto

Dry eye disease (DED) and allergic conjunctivitis affect a large number of patients, and many patients usually have both symptoms. We investigated the interactions between DED and allergic conjunctivitis in mice. Four experimental groups were compared: control, DED, allergy, and allergy with DED. DED was induced by removing the extraorbital lacrimal glands of the mice. Allergic conjunctivitis was induced by intraperitoneal administration of ovalbumin and antigen eye drops. The early phase reaction of the allergy was evaluated using the clinical score, scratching behavior, and vascular permeability in the conjunctiva. Epithelial barrier function was assessed by an LC-biotin assay. Tear fluid volume and corneal fluorescein staining decreased in the DED and allergy with DED groups. LC-biotin penetrated the entire epithelium of both the cornea and conjunctiva in DED mice. The clinical score of the early phase reaction was higher in allergy-induced mice than in non-allergy mice. Edema of the eyelid and conjunctiva were aggravated in mice with DED. The number of scratching episodes and leakage of Evans blue into the conjunctiva were higher in allergy-induced DED mice than in control mice. The presence of aqueous-deficient dry eye caused ocular surface epithelial damage and exacerbated allergic signs and symptoms.

Severe ocular allergic diseases, such as atopic keratoconjunctivitis and vernal keratoconjunctivitis, cause severe allergic inflammation in the conjunctiva and corneal epithelial damage, resulting in visual disturbances. The involvement of damage (danger)-associated molecular patterns (DAMPs/alarmins) in the pathogenesis of these diseases has been recognized. Alarmins released from damaged corneal epithelial cells or eosinophils play a critical role in the induction of corneal lesions, vicious loop of corneal injury, and exacerbation of conjunctival allergic inflammation. Alarmins in the conjunctiva also play an essential role in the development of both allergic inflammation, based on the acquired immune system, and type 2 inflammation by innate immune responses in the ocular surface. Therefore, alarmins may be a potentially important therapeutic target in severe refractory ocular allergic diseases.

We investigated the prophylactic and therapeutic effects of the oral administration of transgenic rice seeds expressing a hypoallergenic Bet v 1 derivative of allergic birch pollen conjunctivitis in mice. Transgenic rice seed depositing a chimeric molecule called TPC7 (tree pollen chimera 7) created by DNA shuffling of Bet v 1 family sequences from birch, alder and hazel in protein bodies of endosperm was generated. BALB/c mice were sensitized to birch pollen in alum and challenged with pollen in eyedrops. They were fed TPC7 transgenic or non-transgenic (control) rice seeds for 14 d before sensitization (prophylactic protocol) or 17 d after sensitization (therapeutic protocol). The clinical score and number of conjunctival eosinophils were significantly lower in TPC7-fed mice than in the control mice based on both the prophylactic and therapeutic protocols. Serum concentration of allergen-specific IgE did not differ between TPC7-fed and control groups in either protocol. Prophylactic administration of TPC7 downregulated the production of IL-4 and IFN-γ, whereas therapeutic administration of TPC7 upregulated the production of IFN-γ by allergen-stimulated splenocytes. Prophylactic or therapeutic oral administration of transgenic rice expressing TPC7 suppressed birch pollen-induced allergic conjunctivitis in mice. Feeding transgenic rice is a potentially effective approach as an allergen-specific immunotherapy for allergic conjunctivitis.

Relapsing polychondritis (RPC) is a rare systemic immune-mediated disease characterized by recurrent inflammation of cartilaginous and proteoglycan-rich tissues throughout the body. Auricular, nasal, tracheal, and articular chondritis and arthritis are common systemic symptoms in patients with RPC. Ocular tissues are also targets of inflammation in RPC, and a variety of ocular symptoms are observed in approximately half of the patients with RPC. Scleritis/episcleritis, uveitis, and conjunctivitis are common symptoms associated with RPC. Less frequently, keratitis, retinopathy, optic neuropathy, muscle palsy, and orbital inflammation are also observed. Ocular inflammation could also be the first manifestation of RPC. Although RPC is a potentially fatal and sight-threatening disease, the rarity of the disease and its protean clinical presentation may lead to delayed diagnosis or misdiagnosis. Given the high prevalence of ocular involvement in RPC, to avoid misdiagnosis, physicians should be suspicious of RPC when they see patients with recurrent ocular inflammatory conditions and various systemic symptoms. In this article, we provide a comprehensive review of ocular manifestations associated with RPC.

Post-operative endophthalmitis caused by Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Therefore, novel alternative treatments that are effective against enterococcal endophthalmitis are required. Bacteriophage therapy has the potential to be an optional therapy for infectious diseases. Therefore, we investigated the therapeutic potential of three newly isolated enterococcal phages, phiEF7H, phiEF14H1, and phiEF19G, in E. faecalis-induced endophthalmitis. These phages could lyse the broad-range E. faecalis, including strains derived from endophthalmitis and vancomycin-resistant E. faecalis in vitro, as determined by the streak test. Morphological and genomic analyses revealed that these phages were classified into the Herelleviridae genus Kochikohdavirus. The whole genomes of these phages contained 143,399, 143,280, and 143,400 bp, respectively. Endophthalmitis was induced in mice by injection of three strains of E. faecalis derived from post-operative endophthalmitis or vancomycin-resistant strains into the vitreous body. The number of viable bacteria and infiltration of neutrophils in the eye were both decreased by intravitreous injection of phiEF7H, phiEF14H1, and phiEF19G 6 h after injection of all E. faecalis strains. Thus, these results suggest that these newly isolated phages may serve as promising candidates for phage therapy against endophthalmitis.

Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required.

A number of drug-releasing contact lenses are currently being studied to address issues inherent in eye drops as a drug delivery method. In this study, we developed epinastine hydrochloride-releasing daily soft contact lenses for treatment of allergic conjunctivitis and examined their in vitro and in vivo performance. Preformed soft contact lenses with/without ionic functional groups were soaked in a solution of epinastine hydrochloride in phosphate-buffered saline to prepare epinastine hydrochloride-releasing soft contact lenses. Among these contact lenses with different ionicities, anionic lenses demonstrated the maximum, relatively linear epinastine hydrochloride release, in vitro. The amount of epinastine hydrochloride release was directly proportional to the concentration of the epinastine hydrochloride solution used to prepare the contact lens. The epinastine hydrochloride-releasing anionic soft contact lens also demonstrated prolonged drug release and significantly greater efficacy compared with epinastine hydrochloride eye drops 12 h after treatment, in vivo. Further studies are required to determine the appropriate amount of epinastine hydrochloride to be contained in the anionic soft contact lenses.