Total Outflow Facility in Live C57BL/6 Mice of Different Age

Abstract

Purpose: To characterize total outflow facility across the live adult mouse lifespan as a reference for mouse glaucoma studies and the common C57BL/6 background strain. Methods: Microperfusion was performed by single-needle cannulation and feedback-controlled coupling of pressure and flow to maintain a constant pressure in the anterior chambers of live C57BL/6NCrl mice aged 3-4 months (n = 17), 6-9 months (n = 10), and 23-27 months (n = 12). This mouse age range represented an equivalent human age range of young adult to elderly. We characterized the following across age groups in vivo: (1) outflow facility based on constant pressure perfusion in a pressure range of 15-35 mm Hg, (2) perfusion flow rates, and (3) anterior segment tissue histology after perfusion. Thirty-nine live mice underwent perfusion. Results: Pressure-flow rate functions were consistently linear for all age groups (all R² > 0.96). Total outflow facility in mice aged 3-4, 6-9, and 23-27 months was 0.0066, 0.0064, and 0.0077 μL/min/mm Hg, respectively. Facility was not significantly different between age groups (all p > 0.4). The groups had closely overlapping frequency distribution profiles with right-sided tails. Post hoc estimates indicated that group facility differences of at least 50% would have been detectable, with this limit set mainly by inherent variability in the strain. A trend toward higher perfusion flow rates was seen in older mice aged 23-27 months, but this was not significantly different from that of mice aged 3-4 months or 6-9 months (p > 0.2). No histological disruption or difference in iridocorneal angle or drainage tissue structure was seen following perfusion in the different age groups. Conclusion: We did not find a significant difference in total outflow facility between different age groups across the live C57BL/6 mouse adult lifespan, agreeing with some human studies. The possibility that more subtle differences might exist ought to be judged with respect to the heterogeneity in facility at different ages. Our findings provide reference data for live perfusion studies pertaining to glaucoma involving the C57BL/6 strain.

Aging and intraocular pressure homeostasis in mice

“…This would result in a shunting of flow from the unconventional to the conventional outflow tract [65], which in turn would require an increase in facility to maintain a desired IOP. Such an increase is consistent with two previous studies that examined outflow facility in aging mice; each reported an increase, or a trend towards an increase, in outflow facility in 3 of 4 strains studied, including C57 mice [66,67].…”

Aging and intraocular pressure homeostasis in mice

“…Gabelt et al, 2003), which in turn would require an increase in facility to maintain a desired IOP. Such an increase is consistent with two previous studies that examined outflow facility in aging mice; each reported an increase, or trend towards an increase, in outflow facility in three of four strains studied, including C57 mice (Millar et al, 2015;Yelenskiy et al, 2017).…”

Effect of a fixed combination of ripasudil and brimonidine on aqueous humor dynamics in mice

“…In addition, the results of the present study suggested that brimonidine also may enhanced outflow facility. Although there is a concern that the outflow pathway after TM may be different from normal due to the slightly higher intraocular pressure used in our two-level constant pressure method, there have been several previous studies using similar methods [54][55][56] and studies examining the correlation between IOP values and outflow facility measurements have shown that linearity is maintained within the range of IOP values used in this study 57 . So far, several methods have been reported for the measurement of outflow facility in the past, but there are several factors that can affect the results of each method 58,59 and no uniform method has been established.…”