Biology subjects

Kuwajima, T.

Publications and source records attributed to Kuwajima, T..

3 recordsLinked to original sources

bioRxiv2026

Wavelet Transform improves time-frequency characterization of the Electroretinographic Oscillatory Potentials as compared to Short-Time Fourier Transform across experimental and clinical models

Purpose: To compare continuous wavelet transform (CWT) and short-time Fourier transform (STFT) analyses of the oscillatory potentials (OPs) of the dark-adapted full-field electroretinogram (FFERG). Methods: FFERG recordings from Royal College of Surgeons (RCS) and healthy Brown Norway (BN) rats, wild-type and Atoh7 enhancer-knockout (KO) mice, and patients with diabetic retinopathy and healthy controls were analyzed with STFT and with CWT employing the real Morlet wavelet, after 60 Hz high-pass and sharp 60 Hz notch filtering. Time- and frequency-localized OP features were quantified and the methods compared on detection of transient OP signals. Both were additionally validated using synthetic OP-like bursts of known frequency embedded in each cohort's recorded noise. Results: CWT revealed distinct time-frequency patterns and disease-specific OP alterations across all rat, mouse, and human cohorts, with improved temporal localization and frequency resolution, whereas STFT merged transient features and was more susceptible to noise. CWT-derived dominant-frequency differences reached significance in all three models; the corresponding STFT difference reached significance only in rats (separate tests; methods not directly compared). In synthetic bursts, both methods recovered injected frequencies to within 1-2.5 Hz, but only CWT resolved two bursts separated by 15 ms. Conclusions: CWT employing the real Morlet wavelet provides a robust, physiologically relevant evaluation of OPs, with improved temporal localization and reduced spectral dispersion relative to STFT in clinical and experimental settings. Translational Relevance: CWT analysis may improve the characterization of inner retinal dysfunction by preserving transient OP time-frequency structure, as illustrated in preclinical rodent models and diabetic retinopathy patients.

physiology↗

bioRxiv2025

Zebrafish optic nerve injury results in systemic retinal ganglion cell dedifferentiation

Retinal ganglion cells (RGCs) are the sole projection neurons connecting the retina to the brain and therefore play a critical role in vision. Death of RGCs during glaucoma, optic neuropathies and after ocular trauma results in irreversible loss of vision as RGCs do not regenerate in the human eye. Moreover, there are no FDA approved therapies that prevent RGC death and/or promote RGC survival in the diseased or injured eye. There is a critical need to better understand the molecular underpinnings of neuroprotection to develop effective therapeutic approaches to preserve damaged RGCs. Unlike in mammals, RGCs in zebrafish are resilient to optic nerve injury, even after complete transection of the optic nerve. Here, we leveraged this unique model and utilized single-cell RNA sequencing to characterize RGC responses to injury and identify putative neuroprotective and regenerative pathways. RGCs are heterogeneous and studies in mice have shown that there is differential resiliency across RGC subtypes. Our results demonstrated that all RGC subtypes are resilient to injury in zebrafish. Quantifying changes in gene expression revealed the upregulation of progenitor and regenerative markers in all RGC subtypes after injury as well as distinct early and late phases to the injury response. This shift in gene expression causes injury-responsive RGCs to resemble RGC subtype 3, a low frequency population of endogenous immature RGCs that are normally maintained in the wild-type, uninjured adult retina. A similar but restricted transcriptomic injury response in RGCs of the uninjured contralateral eye was also detected, highlighting a systemic RGC response to unilateral optic nerve injury. Taken together, these results demonstrate that zebrafish RGCs dedifferentiate in response to injury, and this may be a novel mechanism mediating their unique cell survival and regenerative capabilities. Author SummaryRetinal ganglion cells (RGCs) connect the eye to the brain and are essential for vision. Their death in conditions like glaucoma, affecting over 70 million people worldwide, leads to permanent blindness, with no FDA-approved treatments to prevent it. Unlike mammals, zebrafish RGCs are resilient to optic nerve injury. In this study, we used next-generation sequencing technologies to characterize the RGC response to optic nerve injury at the single-cell level. We discovered that all zebrafish RGCs survive damage by temporarily shifting into a less mature state, resembling a rare population of immature RGCs found in uninjured animals. We identified many genes whose expression changes early or late in the injury response as well as a similar but restricted transcriptomic injury response in the uninjured contralateral RGCs, highlighting the systemic RGC response to optic nerve injury. This work is significant because our detailed characterization of RGC responses to optic nerve injury identifies dedifferentiation as an injury response, possibly important for cell survival and axon regrowth. The genes and pathways we identify are potential therapeutic targets to enable RGC survival in the injured or diseased human eye.

neuroscience↗

bioRxiv2021

Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina

Visual information is transmitted from the eye to the brain along the optic nerve, a structure composed of retinal ganglion cell (RGC) axons. The optic nerve is highly vulnerable to damage in neurodegenerative diseases like glaucoma and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities and here, utilizing an optic nerve transection (ONT) injury and an RNA-seq-based approach, we identify genes and pathways active in RGCs that may modulate their survival. Through pharmacological perturbation, we demonstrate that JAK/STAT pathway activity is required for RGC survival after ONT. Furthermore, we show that immune responses directly contribute to RGC death after ONT; macrophages/microglia are recruited to the retina and blocking neuroinflammation or depleting these cells after ONT rescues survival of RGCs. Taken together, our results support a model in which pro-survival signals in RGCs, mediated by JAK/STAT signaling, counteract the activity of innate immune responses to modulate RGC vulnerability and resilience in the zebrafish retina after severe optic nerve damage.

neuroscience↗