The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice

Abstract

Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.

Comparative Analysis of Age-Related Changes in Lacrimal Glands and Meibomian Glands of a C57BL/6 Male Mouse Model

“…For the tear secretion test, phenol red-impregnated cotton threads (FCI Ophthalmics, Pembroke, MA, USA) were inserted into the lateral canthus of mice for 60 s. The amount of secreted tears was determined by measuring the length of the wet thread in millimeters. The weights of LG were measured and divided by the body weight to adjust the aging-related confounding factor based on a previous study protocol [5,[35][36][37], and tear secretion was also divided by body weight before comparison [5,38].…”

Why Chain Length of Hyaluronan in Eye Drops Matters

“…The mucin Muc5AC mRNA expression was significantly higher under hylan A treatment, indicating a better intrinsic lubrication efficacy of the animals' own tears. Moreover, the density of infiltrated dendritic (inflammatory) cells was significantly lower after treatment with hylan A eye drops than under any other treatment [20]. These results underline the necessity to differentiate hyaluronan eye drops on the basis of their average molecular weight.…”

“…Kojima and colleagues recently reported that hylan A containing eye drops, but not LMW HA containing eye drops preserve the tear volume and Muc5AC secretion under environmental stress in a mouse dry-eye model [20]. The most likely mode of action is the hylan A mediated protection of the lacrimal glands and goblet cells against T cell-mediated damage.…”

“…To prove the hypothesis that hylan A is improving the wettability of and stabilizing the ocular surface epithelium, commercially available eye drops containing 0.15% hylan A (Comfort Shield, i.com medical, Munich, Germany) were tested by Kojima and colleagues [20]. This research group has established an animal model employing environmental dry eye stress (EDES) that mimics the air conditioning stress of visual display terminal work by exposing the animals for five hours daily over a period of three days to air blow from a fan.…”

“…Recently published clinical results seem to indicate that very high molecular weight hyaluronan eye drops do not only act as water binding lubricants, but may actively target the underlying pathophysiological mechanisms of ocular surface disease [19,20]. In the following the current understanding of ocular surface homeostasis will, therefore, be summarized, and the molecular weight dependent physical properties of hyaluronan eye drops be discussed, proposals for terminology of molecular weight and classification of hyaluronan eye drops will be provided, and the concept of mucoadhesion based on entanglement between hyaluronan and mucus molecules will be illuminated.…”