Purpose: To evaluate the efficacy of topical dasatinib and axitinib for treating experimentally induced corneal neovascularization (CNV) in a mouse alkali burn model, and to compare these treatments to established therapies like dexamethasone and bevacizumab. Methods: Thirty-six C57BL/6; 129 Sv mice underwent a standardized alkali burn to induce CNV in both eyes by applying a paper disc soaked in 1M NaOH to the cornea for 20 seconds. The mice were randomly assigned to one of 6 treatment groups: saline (0.9% sodium chloride), DMSO (5%), dexamethasone (0.1%), bevacizumab (0.5%), dasatinib (0.5%), or axitinib (0.5%). Treatments were applied topically 3 times daily. After 2 weeks of treatment, the mice were sacrificed. CNV assessments, including corneal neovascularization area (CNA), vessel length index (VLI), and limbus vasculature thickness, were conducted postmortem using corneal flat-mounts stained with a CD31 antibody for immunohistochemistry. Results: Dexamethasone proved the most effective in inhibiting alkali burn–induced CNA (P < 0.0001), with bevacizumab showing comparable efficacy (P < 0.001). Axitinib also effectively reduced CNA (P < 0.001) and VLI (P < 0.01). In contrast, dasatinib did not significantly reduce CNA (P = 0.74) or VLI (P = 0.98). All eyes in the dexamethasone group developed cataracts compared with 25%–41.7% in the other groups. Conclusions: Axitinib reduced CNA and VLI, although not as effectively as other established treatment modalities, whereas dasatinib did not demonstrate significant effects.

Four different amino acid substitutions have been reported at the p.Asn666 position in platelet‐derived growth factor receptor β (PDGFRβ): p.Asn666Lys, p.Asn666Tyr, p.Asn666Ser, and p.Asn666His. All four substitutions result in strikingly different phenotypes, ranging from somatic infantile myofibromatosis in p.Asn666Lys and ocular pterygium–digital keloid dysplasia in p.Asn666Tyr to a severe form of Penttinen syndrome in p.Asn666Ser, while p.Asn666His is associated with a complex phenotype characterized by debilitating hand and foot contractures and facial coarseness. Here, we show that the p.Asn666Lys, p.Asn666Tyr, and p.Asn666His substitutions result in increased total PDGFRβ phosphorylation at 32°C compared to 37°C. All four substitutions exhibit distinct activation patterns of specific PDGFRβ tyrosine residues at both temperatures, indicating a unique activation of each variant. The temperature effect on downstream signaling is present across all substitutions, resulting in substitution‐specific downstream signaling at both 37°C and 32°C. This complex interplay of downstream signaling proteins could be important for the clinical manifestations of p.Asn666 PDGFRB variants. Furthermore, variant‐specific overactivation of tyrosine residues and downstream signaling at 32°C emphasize the importance of temperature as an environmental factor in the pathogenesis of this diverse group of disorders.

Background: Norepinephrine is commonly used during acute burn resuscitation to maintain adequate perfusion pressure. However, its effects, together with the burn-induced catecholamine surge, on arterial α₁-adrenergic receptors (α₁-AR) remain unclear. This study examined whether burn injury and continuous norepinephrine infusion alter arterial α₁-AR subtype expression at the transcriptional and protein levels. Methods: Sprague–Dawley rats were randomized to full-thickness scald burn involving 25% total body surface area with continuous intravenous norepinephrine or sodium chloride (NaCl) infusion, sham injury with norepinephrine infusion, or untreated controls. Mean arterial pressure (MAP) was measured at baseline and before euthanasia (six or 24 h). Aorta, carotid, and renal arteries were collected for analysis of α₁-AR subtypes (Adra1a, Adra1b, and Adra1d) using quantitative PCR (qPCR) and immunohistochemistry (IHC). Results: Norepinephrine efficiently increased MAP in sham animals. In burned animals with norepinephrine, MAP increased at six hours (+10.6 mmHg) but fell below baseline at 24 h (−6.4 mmHg). Burned animals given NaCl had persistently lower MAP than those given norepinephrine, at six hours (−19.1 mmHg) and 24 h (−21.1 mmHg). qPCR demonstrated significant downregulation of Adra1b in the renal artery across all groups compared to control (7.8–16.4-fold, p < 0.001). Overall, changes in protein expression across different vascular beds and receptor subtypes were inconsistent. Conclusions: Norepinephrine increased MAP in both sham and burned animals, confirming the drug’s efficacy. Burn injury and sustained norepinephrine exposure were associated with early, vessel-specific alterations in α₁-AR mRNA expression. The absence of consistent protein-level changes within 24 h suggests a delay in receptor expression on protein level.