Keratinocyte growth factor-2 (KGF-2), an effective agent in the development of epithelial tissue and regeneration during corneal wound healing, is a potential therapeutic option to treat the corneal diseases with corneal epithelial defects. However the tissue distribution and pharmacokinetics of KGF-2 have not been explored yet in eye upon topical application. Using (125)I-labeled recombinant human KGF-2 ((125)I-rhKGF-2), tissue distribution of rhKGF-2 in alkali-burned and control rabbit eyes was studied. Our results revealed that (125)I-rhKGF-2 was distributed to all eye tissues examined. The highest radioactivity level was found in the cornea, followed by iris, sclera, ciliary body, lens, aqueous humor, vitreous body, and serum in a greatest to least order. The levels of (125)I-rhKGF-2 were higher in corneas of alkali-burned eyes than those in control eyes though without statistical significance. Calculated pharmacokinetic parameters of t1/2, Cmax, and Tmax of rhKGF-2 in the rabbit corneas were 3.4 h, 135.2 ng/ml, and 0.5 h, respectively. In iris, lens, aqueous humor, and tear, t1/2, Cmax, and Tmax values were 6.2, 6.5, 5.2, and 2.5 h; 23.2, 4.5, 24.1, and 29,498.9 ng/ml; and 1.0, 0.5, 0.5, and 1.0 h, respectively. Predominant and rapid accumulation of rhKGF-2 in corneas suggests that therapeutic doses of rhKGF-2 could be delivered by topical application for treatment of corneal diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.exer.2015.05.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Drug Development.
Alzheimers Dement
December 2024
University of Florida / Center for Translational Research in Neurodegenerative Disease, Gainesville, FL, USA.
Background: Vaxxinity is developing an active immunotherapy targeting Tau for Alzheimer's disease (AD) and other tauopathies. VXX-301 is a multi-epitope vaccine designed to target the N-terminal and repeat domains of Tau. This design enables targeting multiple forms of Tau thought to contribute to Tau associated pathologies.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
L & J Bio, Co., Ltd, Seoul, Songpa-Gu, Korea, Republic of (South).
Background: Neurofibrillary tangles (NFTs), along with amyloid beta plaque, are neuropathological aggregates of Alzheimer's Disease (AD). Hyperphosphorylated tau is responsible for the NFTs formation and further neurodegeneration in AD. The hippocampal region and the entorhinal cortex (EC) have been a major focus of AD research because the deposits of hyperphosphorylated tau protein and NFT in these regions are correlated with memory deficits.
View Article and Find Full Text PDFBackground: VY-TAU01 is a recombinant humanized IgG4 monoclonal antibody (mAb) directed against pathological tau for the treatment of patients with mild dementia or mild cognitive impairment due to Alzheimer's disease (AD). Both VY-TAU01 and its parental mouse IgG1 mAb Ab-01 target an epitope in the C-terminus of tau, bind pathological tau with high affinity and selectivity over wild-type tau, block paired helical filament seed-induced tau aggregates in vitro, and selectively stain tau tangles in AD and P301S mouse (C57/B6J-Tg[Thy1-MAPT*P301S]2541Godt) brain. Ab-01 robustly inhibits seeding and propagation of pathological tau in a P301S mouse seeding model.
View Article and Find Full Text PDFBackground: Homozygosity for the rare APOE3-Christchurch (APOE3Ch) variant, encoding for apoE3-R136S (apoE3-Ch), was linked to resistance against an aggressive form of familial Alzheimer's disease (AD). Carrying two copies of APOE3Ch was sufficient to delay autosomal AD onset by 30 years. This remarkable protective effect makes it a strong candidate for uncovering new therapies against AD.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Switch laboratory, VIB - KU Leuven Center for Brain & Disease Research, Leuven, Belgium.
Background: Pathological tau accumulation is the primary constituent of neurofibrillary tangles and other tau aggregates seen in various neurodegenerative diseases collectively known as tauopathies. Recently, immunotherapeutic strategies focused on tau have shown promise in reducing tauopathy in both cellular and animal models.
Method: We previously used humanized yeast models to purify recombinant hyper-phosphorylated human Tau for mouse immunizations and the isolation of a high-affinity anti-Tau monoclonal antibody (mAb) with enhanced diagnostic and prognostic capacities.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!