Abstract
Purpose :
To develop and evaluate a method for producing unilateral controlled elevation of IOP (CEI) in awake freely-moving rats.
Methods :
Silicone tubing attached to a microcannula (0.005” ID, 0.010” OD, Ingenarious) was passed subconjunctivally from the limbus through the orbital septum to a Pinport (Instech) attached to the skull, allowing intermittent connection to a BSS-containing reservoir and transducer. The microcannula was inserted through a small scleral incision posterior to the limbal vascular plexus, where it self-directed into the posterior chamber. It was fixated with nylon sutures to the limbal sclera. In (n=5) rats, IOP was evaluated unilaterally under anesthesia by raising the reservoir from 30 to 60 mm Hg in 10 mm increments, with Tonolab IOP taken at each pressure level. IOP values were compared by Bland-Altman analysis. In another group (N=10), reservoir IOP was elevated to 40 mmHg for 4–7 hours. Tonolab IOP was determined every 30 minutes and linear regression used to assess IOP stability.
Results :
Overall, cornea and lens clarity following implantation (N=29) was unaffected for as long as 9 weeks. Comparison of Tonolab vs reservoir pressures, monitored up to 6 weeks, revealed a Bland-Altman bias of 1 ± 5 mmHg, indicating good measurement agreement. Tonolab IOP was stable over 4-7 hours (by linear regression) in 8 out of 10 animals (P>.06, Figure 1A). Direct anterior chamber IOP readings using a second transducer in one animal 6 weeks after implantation showed excellent agreement with the BSS reservoir transducer. (Figure 1B)
Conclusions :
A Pinport-connected, indwelling microcannula remains functional for weeks and can allow accurate, periodic, sustained CEI exposures. When combined with a tether system for BSS delivery, no anesthesia will be needed. This experimental method can be used in awake rats to mimic IOP fluctuations commonly seen in human glaucoma.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.