Association between axial length and HDL in children: a hospital-based cross-sectional study

In our study, we found that there was a statistically significant difference in the HDL level between Group A (axial length < = 23 mm) and Group B (23 mm < axial length < = 24 mm). Group A had higher levels of HDL than Group B. It was also found that Group A had a considerably higher concentration of HDL than Group C (axial length > 24 mm). There was a statistically significant negative correlation between axial length and HDL levels.

Few studies have studied the association between axial length and HDL. The main protein component of HDL, apolipoprotein A-I (apoA-I), controls its size and structure, solubilizes its lipid components, removes cholesterol from peripheral cells, activates the LCAT enzyme, and transports the resultant cholesterol esters to the liver [23‐25]. Most studies involve HDL put their attention on apoA-I due to its significance in the structure and function of HDL.

In 2006, Bertrand et al. revealed the “GO/GROW” and “STOP” signals in regulating eye growth [26]. The “GO/GROW” signal is believed to accelerate axial elongation, while the “STOP” signals is deemed to stop or prevent the growth of axial length. They demonstrated that apoA-I was capable of inhibiting excessive ocular axial growth, which enabled it to perform the function of a STOP signal. They have proved that apoA-I exhibits a STOP profile in both the retina and the fibrous sclera, and ocular axial elongation could be inhibited by up-regulating apoA-I. It is assumed that PPAR-α agonists increase the expression of apoA-I, the HDL lipoproteins’ main protein component, through transcriptional pathways [27, 28]. Numerous earlier investigations confirmed that PPARs positively regulated apoA-I. According to a research by Gervois et al., hepatic apoA-I and apoA-II expression was induced by PPAR-α activation, and this boosted plasma HDL cholesterol in humans [28]. It has also been demonstrated that PPAR-D can boost apoA-I and high-density lipoprotein production via activating the ATP-binding cassette transporter 1 (ABCA1) gene [29]. The findings of these investigations provided support for the hypothesis that apoA-I might be a common downstream target for the PPARs.

Plasminogen and Wnt pathways are two potential relevant signaling cascades that could be involved in regulating ocular axial development downstream of apoA-I [30, 31]. Through its inhibition of the plasminogen pathway, apoA-I may function as a STOP signal, deactivating matrix metalloproteinases and TGF-β and preventing their activation. There is a correlation between the attenuation of TGF-β and axial elongation [30]. Additionally, apoA-I has the potential to influence plasminogen activation via the low density lipoprotein receptor (LDLR) family [32]. On the other hand, Wnt signal transduction pathway plays a vital role in the development of the eye by the coreceptors [33, 34]. It is well established that MFRP (membrane Frizzled-related protein) is connected to the Wnt binding cysteine-rich domain of the frizzled family of transmembrane proteins [35]. These proteins are competitive inhibitors of Wnt signaling, which is an important mechanism in the formation of the vertebrate eye. These findings provide evidence that apoA-I plays a role in the transmission of the STOP signal, which supports the hypothesis that apoA-I is involved in this process.

There are some effective ways to raise the levels of HDL cholesterol. Getting more physical activity, losing extra weight, choosing healthier fat (monounsaturated and polyunsaturated fats), drinking moderate amounts of alcohol, stopping smoking, are demonstrated to be helpful in boosting HDL cholesterol.

This study was carried out within the scope of Hangzhou, a southern city in China, involving the analysis of children, which can be an epitome for the analysis of ocular status. As far as we know, no definite research was designed to study the association between HDL and axial length. Hence, the result in our study, negative correlation between axial length and HDL levels, may bring the HDL levels in the population of teenagers to the attention of ophthalmologists.

However, our study had some limitations. First and foremost, since our study is based on a cross sectional research, we can not determine whether there is a causal relationship between axial length and HDL or not. Also, the data in our study is gained from a single hospital, which may have a regional bias on the result. Furthermore, due to the fact that our study only included a limited number of kids, further large multicenter randomized controlled study is needed to assess the association and causal relation between axial length and HDL in children.