Intracameral Sodium Hyaluronate Injection Induces a Delayed Spike in IOP and RGC Death in Rats: Implications for Post-operative Care After Cataract Surgery

Abstract

 

Purpose:

 

Acute rises in intraocular pressure (IOP) are often seen after ocular surgery, a condition exacerbated by the injection of sodium hyaluronate, a viscoelastic compound that is routinely injected during some ocular procedures. IOP spikes following surgery have been reported but their correlation with retinal ganglion cell (RGC) death has not been studied. In this study we aimed to: 1) develop a rodent model of acutely raised pressure using intracameral injections of sodium hyaluronate to induce an acute rise in IOP, and 2) correlate the spikes in IOP with RGC death. This translational model will be useful to test candidate RGC neuroprotective treatments.

 

Methods:

 

Male Sprague Dawley rats (n=4) had unilateral intracameral injections of 15µl 2.4% sodium hyaluronate and IOP was measured by tonometry on 7 consecutive days and compared to readings from contralateral intact eyes. RGC were retrogradely labelled with 4% FluoroGold™ (FG) 48 hours before retinae were harvested at 14 days post-injection for FG-filled RGC counts in retinal whole mounts.

 

Results:

 

A single intracameral injection of 2.4% sodium hyaluronate led to an increase in IOP that peaked at 19.0±1.2mmHg (± standard error) giving an increase from baseline of 88±12% at day 4 (Figure 1). This delayed IOP spike was associated with 29±4% RGC death at 14 days compared to controls (p<0.01) (Figures 2 and 3).

 

Conclusions:

 

The delayed 88% increase in IOP seen in this rodent model was associated with 29% RGC death, losses that would impact on visual acuity. Similar acute IOP increases are reported in humans but no observations are reported at late post-surgery time points indicating the need for clinical studies to evaluate retinal function post-surgery. Our acute model of increased IOP and RGC loss seems comparable to observations in humans and will provide a useful translational model to test the efficacy of novel neuroprotective drugs.  

 

Keywords: intraocular pressure • neuroprotection • retina