Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.11.04.764222

Failed allogeneic corneal lenticules show fibrosis and identity loss without dominant T cell rejection

Jiang, H.·Di, Y.·Li, C.·Jiang, Y.·Li, Y.·Zhou, Y.
View original source ↗Export metadata ↓

Abstract

Failed allogeneic corneal stromal lenticules develop progressive opacity, but the state of the implanted tissue is unknown. Here we show that six explants from three patients occupy a fibrotic integration-failure state with scar-matrix production and loss of corneal identity without a dominant T cell rejection program. Scar-matrix, transparency and corneal-identity programs separated every patient from eight unimplanted donor controls, the last defined by independent human single-cell references. Calibrated immune programs and repertoire reconstruction distinguished the explants from canonical adaptive rejection. Exchange reduced interface reflectivity initially, followed by recurrent opacity in two patients and corneal steepening with declining uncorrected acuity in the third. In non-scarring rabbit repair, identity moved toward the uninjured state as backscatter returned toward normal despite increasing similarity to the explant-derived expression signature. Within one culture experiment, marked scar suppression accompanied opposite identity responses. Tacrolimus and rapamycin likewise suppressed canonical rejection while moving identity in opposite directions. Resveratrol combined reduced scar-associated programs and increased identity with improved graft appearance in the source study. These findings establish classic-rejection activity and tissue integration as separable axes and direct treatment of failed lenticules from escalating immunosuppression toward control of stromal remodeling and preservation of corneal identity.

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jiang, H., Di, Y., Li, C., Jiang, Y., Li, Y., Zhou, Y.. 2026-11-05. Failed allogeneic corneal lenticules show fibrosis and identity loss without dominant T cell rejection. https://doi.org/10.64898/2026.11.04.764222

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Transmural Single-Nucleus Transcriptomics Nominates Candidate Disease Programs in Human Necrotizing Enterocolitis

Background & Aims: Necrotizing enterocolitis (NEC) is a life-threatening disease of premature infants marked by inflammation, ischemia, mucosal injury, and, in advanced cases, necrosis extending into deeper layers of the intestinal wall. Because NEC affects specialized, interacting cells in a developing intestine, we used single-nucleus transcriptomics to build a transmural, cell-type-resolved map and nominate hypothesis-generating disease programs distinct from maturation. Methods: Full-thickness intestinal specimens from fetal/prenatal controls, acute NEC cases, and infant controls were analyzed by single-nucleus RNA sequencing (snRNA-seq). Fetal and infant samples served as developmental references. Analyses included cell annotation, NEC-versus-infant differential expression, gene ontology (GO), cross-lineage recurrence, cell death signatures, and developmental maturity. Results: We profiled 53,735 nuclei by snRNA-seq and resolved 34 epithelial, stromal, vascular, immune, neuronal, glial, and smooth muscle populations. We used a morphology-based nuclei scoring system for sample selection that predicted high-quality transcript recovery. NEC nuclei were represented across this cellular landscape, with recurrent gene-expression changes suggesting shared inflammatory recruitment, antimicrobial/redox defense, stress adaptation, complement/vascular activation, reduced homeostatic signaling, and cell death-associated regulation. Developmental maturity analysis identified fetal-like expression levels in subsets of NEC-regulated genes. Proliferative crypt populations retained DNA repair/cell-cycle programs with inflammatory, hypoxic, and ER-stress features, while absorptive enterocytes showed reduced digestive, transport, detoxification, and terminal villus-function programs. Secretory-lineage changes implicated goblet mucus-barrier responses with reduced glycosylation, trafficking, and hydration; enteroendocrine changes in epithelial defense, metabolic stress, and neural signaling; and Paneth cell retention of antimicrobial effector transcripts despite altered ER quality control, autophagy, and granule delivery in NEC. Non-epithelial programs implicated stromal Wnt/BMP niche loss, impaired lymphatic drainage/scavenging, macrophage cytokine activation with reduced clearance machinery, neuroglial circuit defects, and altered smooth muscle contraction-relaxation balance. Conclusions: This single nuclear intestinal cell atlas nominates multicellular programs that may govern NEC initiation, progression toward tissue destruction, and resolution toward functional recovery.

pathology↗
bioRxiv2026

Explainable Multimodal Prognostic Modeling Uncovers New Clinically Relevant Pathological Features in a Multi-Institutional Pancreatic Neuroendocrine Tumor Cohort

Although many patients with a well-differentiated pancreatic neuroendocrine tumor (PanNET) are cured after surgical resection, it is hard to predict outcome in these patients. Current prognostic assessment relies largely on Ki-67 proliferation index, tumor stage, and established adverse pathologic features, such as vascular and perineural invasion. However, individually, these variables incompletely explain why patients with similar clinicopathologic profiles sometimes experience markedly different outcomes. To address this challenge, we assembled three independent cohorts with a surgically resected PanNET. In total, we included 1,438 patients with approximately 30,000 histology images, and approximately 12,000 person-years of follow-up. We separately modeled structured clinicopathologic information with Cox regression and tumor-centered pathology images with deep learning on an internal cohort treated at Johns Hopkins Hospital and performed multimodal continuous-time survival modeling to reveal which clinical and pathologic features are most important in predicting patient outcome. Across Cox models of censored time to recurrence-free survival, a text-based clinicopathological model that incorporated known prognosticators achieved a C-index of approximately 0.87, the image-based histology model approximately 0.80, and decision-level late multimodal fusion approximately 0.88 on the internal test set. The clinical model demonstrated strong prognostic discrimination using established risk factors, mainly relying on the TNM stage and Ki-67 index. Primary tumor histology retained substantial prognostic signal, with analysis restricted to tumor-centered regions to reduce reliance on unrelated tissues that might indirectly indicate disease extent. Interpretation of high-attention image tiles revealed regions of importance in the primary tumor, including recognized adverse morphologic features such as the leading edge of the tumor and foci of vascular or perineural invasion. Unexpectedly, intratumoral and peritumoral stroma accounted for nearly 50% of the model's high-attention regions, suggesting that the stroma may yield equal prognostic information to neoplastic cells in recurrence-prediction models. To test generalizability, we further evaluated the trained models in independent cohorts from two institutions with different demographics, where discrimination varied by site (mean late-fusion C-indices of 0.864 and 0.723). Together with the improved discrimination achieved through late fusion, our findings suggest that current clinicopathologic variables can be modeled to form reliable prognosticators, and that routine hematoxylin and eosin (H&E) stained slides of the primary tumor contain additional prognostically important information not fully captured by conventional clinicopathologic assessment, such that together, the two sources provide complementary information.

pathology↗
bioRxiv2026

Histopathological and virus-associated features of Boid Inclusion Body Disease in Boa constrictor

Boid inclusion body disease (BIBD) is a reptarenavirus-induced fatal disease of boid snakes that, while diagnosed with ease due to the pathognomonic intracytoplasmic inclusion bodies (IB), is not yet fully characterized pathomorphologically and with regards to its pathogenesis. The present study retrospectively investigated a random cohort of 50 captive male and female boa constrictors of variable age (neonate to 25 years) for histopathological changes and in situ viral protein (nucleoprotein, NP, and glycoprotein 2, GP2) expression patterns. IB formation and NP expression were scored semiquantitatively. The vast majority of snakes (42/50; 84%) exhibited histopathological changes; these mainly (39/42; 93%) represented inflammatory processes that most frequently affected the gastrointestinal tract. Overall, IB and NP scores were significantly higher in the more recent cases (2020-2025) compared to the older cases (2000-2003). NP scores did not differ between age groups or sex, but were lower in animals with clinical signs and higher in those with histopathological changes. No statistically significant association was found between NP scores and inflammatory processes, neither in general nor in individual organs. GP2 expression, as an indicator of virion assembly, was less consistent than NP expression and generally restricted to individual cells with and without IBs. There was no histological evidence of overt damage in infected cells. Jointly, the results indicate different phases of restrictive and systemic viral replication that are not directly associated with pathological processes and/or clinical signs.

pathology↗