The ocular tissue is known as immune-privileged; the presence of a blood-tissue barrier and the lack of lymphatic vessels and lymphoid tissues do not allow for steady immune cell recruitment. Therefore, if a "foreign body" invades, the system does not function to eliminate it, rather an immune tolerance to the foreign body is established, allowing it to remain in the ocular tissue. When a foreign body enters the ocular tissue, the microglia are initially activated. Microglia are innate immune cells, and their origin and function remain controversial. We have been addressing this mystery in our own unique way and found an answer. The evidence for the development of intraocular microglia suggests that the eye may establish its unique immune system.
In clinical practice, the ocular tissue's unique immune system is challenged when dealing with foreign bodies that enter the eye. In clinical practice, bacteria are the most hated of all foreign bodies by ophthalmologists. This is because bacteria can cause fatal damage to ocular tissues if they remain and multiply within the eye. Bacterial infection after intraocular surgery is the most critical condition to be avoided. Therefore, rapid and accurate diagnostic methods are needed for bacterial infections in ocular tissues. However, rapid and precise diagnosis of bacterial infection in ocular tissues has yet to be established. This is because the number of specimens is small and antibiotic therapy has already started at the time of specimen collection. Continued treatment without reliable identification of the bacteria may delay recovery and cause severe loss of visual function. Therefore, diagnostic methods for ocular bacterial infections are an unmet need that requires urgent development. The development of new diagnostic methods and the results obtained will allow us to elucidate the pathogenesis of the disease and select appropriate treatment, thereby avoiding catastrophic ocular damage. This presentation will be divided into the following three parts:
I. Exploring a novel diagnostic system for detecting bacterial eye infections
Bacterial endophthalmitis progresses rapidly and can lead to blindness. The diagnosis is made by microscopic examination using gram staining, culture tests, and identification of bacteria by polymerase chain reaction, but the identification rate of bacteria for all these tests is low. Therefore, we will examine whether a microscope equipped with an automatic gram stain analyzer can properly analyze ophthalmic specimens with few pathogens and discuss the advantages and weaknesses of the device. We performed the metagenomic analysis and identified the bacterial species in the vitreous sample from a patient with bacterial endophthalmitis. We also explored the possibility of differentiating bacterial endophthalmitis from uveitis by analyzing the diversity of bacterial flora.
II. Characterization of diseases caused by interrelationship between the ocular infection and host and search for their treatment
Sarcoidosis, classified as a noninfectious form of uveitis, has recently been proposed to be linked with Cutibacterium acnes, a commensal bacterium. Our objective is to elucidate the pathogenesis of uveitis attributed to sarcoidosis and explore potential therapeutic interventions based on the findings from analysis of actual lesion tissues (vitreous fluid), with a particular focus on investigating any potential correlation with commensal bacteria.
III. The study focuses on the elucidation of microglia development associated with the ocular immune system using human induced pluripotent stem (iPS) cell-derived ocular organoids
Microglia are resident immune cells of the central nervous system and are thought to originate from the mesoderm and arise via the yolk sac. Microglia regulate the immunogenicity of the retina. Nevertheless, how microglia develop in the eye remains unclear. We have successfully generated organoids from human iPS cells that mimic human eye development in two dimensions using the self-formed ectodermal autonomous multi-zone (SEAM) method. This study investigates whether microglia can develop within ectoderm-derived SEAM organoids using human iPS and embryonic stem cells. If present, we will analyze whether microglia differ from its previously reported characteristics, single cell RNA sequencing, and cytokine production characteristics to confirm whether they are involved in the ocular immune system.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 128: 256-281, 2024.