Crystalline lens oscillations are commonly observed in eye-tracking data, yet their physical origin remains incompletely understood. While previous studies have primarily attributed these oscillations to oculomotor control or measurement artifacts, increasing evidence suggests a biomechanical contribution from intraocular structures, particularly the lens. In this study, we propose a physics-based framework that models the lens as a damped mass–spring system driven by ocular angular acceleration during saccades. The model predicts the relative mechanical displacement of the lens and captures the inertial displacement and subsequent transient relaxation of the lens, yielding a transient extrema-spacing frequency metric of ∼22 Hz, numerically comparable to experimentally reported post-saccadic lens frequencies, together with peak displacements on the order of ∼0.3 mm and a settling time of ∼70 ms. A systematic parameter analysis shows that both stiffness and damping influence displacement magnitude, while stiffness mainly affects the timing of the transient response and damping governs energy dissipation. Importantly, the settling time exhibits a non-monotonic dependence on the coupled variation of stiffness and damping, highlighting the limitations of one-dimensional parameter analysis. These findings provide a mechanistic interpretation of post-saccadic oscillations as an emergent response of a coupled viscoelastic system. The proposed framework provides a mechanical basis for investigating how lens dynamics may contribute to post-saccadic features observed in eye-tracking measurements, although direct prediction of such signals would require an additional optical or measurement model.
Background Retinitis pigmentosa (RP) represents a degenerative disorder of photoreceptors marked by reactive gliosis and inflammatory processes. This present work aimed to explore how apolipoprotein E (ApoE) influenced the retinal inflammation and to its potential mechanism involved in RP. Methods ApoE levels were measured by ELISA in serum from healthy volunteers and patients with RP and by western blotting in retinas from postnatal day 28 wild-type (WT) and rd10 (Pde6brd10) mice. Retinal inflammation was assessed via cytokine expression and reactive gliosis of glia cells based on RNA-seq, qPCR, and immunofluorescence. ApoE-knockout mouse was used to examine the effect of ApoE on the retinal inflammatory response. A co-culture system of a microglial cell line (BV2 cells) and a Müller glial cell line (QMMuC-1 cells) was established to simulate retinal inflammation in vitro and to explore the effect of ApoE on miR-146a/b and PU.1 expression. Results ApoE levels was increased in the serum of patients with RP and were mainly upregulated in Müller cells of rd10 mice. Reactive gliosis and inflammation were detected in rd10 mice and ApoE knockout mice. In vitro, activated BV2 cells induced ApoE expression in QMMuC-1 cells. ApoE treatment significantly repressed IL-1β and TNF-α expression in both cell types. Mechanistically, ApoE may promote miR-146a/b expression via PU.1, thereby regulating miR-146, critical negative regulators of NF-κB signaling. Conclusions ApoE is compensatorily upregulated to inhibit retinal inflammation though miR-146a/b and may serve as a potential target for the clinical diagnosis and treatment of retinal degenerative disease.
Cell-cycle regulatory perturbations are increasingly implicated in retinal degeneration, yet their biological significance varies fundamentally across retinal cell types because proliferative competence differs between terminally differentiated neurons and proliferation-capable retinal populations. While retinal neurons normally maintain permanent cell-cycle exit, Müller glia, microglia, retinal pigment epithelial (RPE) cells, endothelial cells, and pericytes retain varying capacities for quiescence, proliferation, and injury-induced reactivation. Consequently, alterations in cyclins, cyclin-dependent kinases (CDKs), RB-E2F signaling, DNA replication machinery, or checkpoint regulators may represent distinct biological states depending on cellular context. In this review, we examine cell-cycle perturbations across inherited retinal diseases (IRDs), age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal gliosis and inflammation, and retinal organoid models. We critically assess current evidence for neuronal cell-cycle re-entry and propose a practical evidence hierarchy that distinguishes pathway activation, neuronal localization, progression through cell-cycle phases, cell-type-specific causality, and longitudinal cellular fate. We argue that many reported findings reflect incomplete or ambiguous evidence and should not be equated with bona fide neuronal cell-cycle re-entry. We further propose a fate-bifurcation model in which cellular outcomes are determined by the depth and duration of cell-cycle engagement together with cell identity, checkpoint integrity, CDK inhibitor activity, DNA damage burden, metabolic state, and microenvironment cues. Under this framework, limited or checkpoint-restrained engagement may support transient neuronal adaptation or survival, whereas sustained activation may promote senescence-like states, and deeper progression under inadequate checkpoint control may contribute to neuronal dysfunction and death. In proliferation-competent retinal compartments, related pathways may instead drive gliosis, immune expansion, epithelial remodeling, angiogenesis, or senescence. By integrating evidence across retinal diseases and cell types, this state-based framework provides a unified interpretation of apparently conflicting observations and offers a conceptual foundation for developing cell-type- and state-specific therapeutic strategies for retinal degeneration.
Optical coherence tomography (OCT) enables non-invasive, high-resolution imaging of retinal layers and is widely used to assess structural changes in preclinical models of retinal and optic nerve disease. However, OCT-based retinal thickness measurements in rodents remain insufficiently standardized, with differences in measurement location and segmentation methodology potentially limiting reproducibility and comparability across studies. We describe a standardized OCT-based protocol for ganglion cell complex (GCC) thickness measurement in mice using predefined retinal landmarks and manual segmentation. Six radial OCT scans separated by 30° are acquired around the optic nerve head, and GCC thickness is measured using ImageJ at three nominal radial distances on each side of the optic nerve: 1000, 1500, and 2000 μm. The applicability of the protocol was evaluated in a murine optic nerve crush (ONC) model. GCC thickness decreased significantly over time, from 68.8 ± 5.2 μm at baseline to 60.7 ± 8.0 μm at day 15 and 60.6 ± 9.8 μm at day 24. Radius- and quadrant-specific analyses further demonstrated the ability of the protocol to detect regional patterns of GCC thinning. This protocol provides a structured approach for OCT-based GCC thickness assessment in mice and may improve consistency and comparability across preclinical studies.
