Poster - #VH-67125 - Keywords: Matrix Gla protein MGP Vitamin K distribution Menaquinone-4 MK4 Phylloquinone PK Intraocular pressure IOP Ocular tissue vitamin K Comparative eye anatomy Trabecular meshwork Cross-species vitamin analysis HPLC ocular bioanalysis

Species and Tissue-Specific Distribution of Vitamin K in Ocular Tissues: A Comparative Analysis

Mong, Michael [1]; Fu, Xueyan [2]; Tran, Khoa D. [3]; Booth, Sarah [2]
[1] VA North Texas Health Care System, Dallas, TX, [2] Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, MA, [3] VisionGift, Portland, OR

ABSTRACT:
Abstract Number: 1179 - B0422

MICHAEL MONG*1, Xueyan Fu2, Khoa D. Tran3, Sarah Booth2
1Ophthalmology, VA North Texas Health Care System, Dallas, Texas, United States; 2Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, Massachusetts, United States; 3Research and Development, VisionGift, Portland, Oregon, United States

Disclosures: MICHAEL MONG: Code N (No Commercial Relationship) | Xueyan Fu: Code N (No Commercial Relationship) | Khoa D. Tran: Code N (No Commercial Relationship) | Sarah Booth: Code N (No Commercial Relationship)

Purpose
The vitamin K dependent protein, matrix Gla protein (MGP) has been implicated in the maintenance for physiologic IOP in mice. However, little is known about the content of vitamin K (VK) in the eye. We tested the hypothesis that the VK menaquinone-4 (MK4), and phylloquinone (PK) can be found in human, cow, and mice eyes, vary among species and across ten tissue types, as well as by age and gender, in a pilot cross-sectional observational study.

Methods
MK4 and PK concentrations (pmol/g) were measured in female (69 and 88 y, n=2) and male (34 and 86 y, n=2) eyes from decedent human organ donors, in the eyes of cow (Nebraska Scientific, n=2), and C57BL6 female mice (14 mo, combined n=5) by validated assay using HPLC at Tufts University. Combined trabecular meshwork’s from two cornea donors were also analyzed. Sample preparation was adapted and validated in ocular tissue, yielding an approximate 90% recovery rate of internal standard. The lower limit of detection of both MK4 and PK are 0.1pmol/g.

Results
VK was detected in the eyes of all species analyzed. In humans, both MK and PK was found in the iris-ciliary body, choroid, optic nerve, and retina (MK4: 0.2-39.0 pmol/g; PK: 0.4-6.1 pmol/g). PK was also found in the trabecular meshwork, vitreous humor, and serum, whereas MK4 was not. No PK or MK4 was detected in cornea, lens or aqueous humor. Pooled trabecular meshwork’s contained PK but no MK4. Statistical analysis revealed no significant differences in MK4 or PK concentrations by gender (Mann-Whitney U test: MK4, p=.80; PK , p=0.24) or age (linear regression: MK4, R2=0.002, p=0.78; PK, R2=0.015, p=0.47). Cow eyes contained MK4 in the retina, optic nerve, choroid/RPE, iris-ciliary body, sclera, and aqueous humor (3.4 to 135 pmol/g). No MK4 was detected in the lens or vitreous humor. PK was found only in the optic nerve (4.0 pmol/g). In mice, VK analysis was limited to the retina, RPE/choroid/sclera, cornea, and lens. MK4 was found in the retina (1480 pmol/g) and RPE/choroid/sclera (34 pmol/g). No PK was detected.

Conclusions
Ocular tissue from the three species tested contained VK, with MK4 and PK varying by species and tissue type. No significant association was found between VK concentrations and gender or age. However, the small sample size limits the generalizability of these findings. Further investigation is warranted.

Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details.
Losing one’s sight consistently ranks first among the most feared of conditions. Glaucoma is the leading cause of irreversible blindness in the world, with many documented differences in who gets glaucoma and how severe it becomes. Recent estimates suggest approximately 4.22 million people in the US have glaucoma, often without knowing it. The number of people that have glaucoma increases with age to around 7-8 percent in those 80 years and older. Certain racial groups are 2-3 times more likely to have the disease and to have a more severe form-yet the reasons for many of these differences remain unknown.

Evidence is mounting, that vitamin K (VK) may play an important role in the eye. Recent studies suggest that matrix Gla protein (MGP), a protein that requires VK to work, has a role to play in controlling intraocular pressure, which is often elevated in glaucoma.

Experts acknowledge that nutrition and dietary interventions are powerful ways to modify the risk of and treat diseases across one’s lifetime.

Our study seeks to begin to understand the role VK might be playing in the eye with the hope of finding new ways to reduce and treat glaucoma and other diseases of aging.