Bilateral Serous Retinal Detachment in Lymphoid Blast Crisis of Chronic Myeloid Leukemia.

We herein report a patient with Philadelphia chromosome-positive lymphoid blast crisis of chronic myeloid leukemia (CML), who presented with bilateral serous retinal detachment (SRD). A 36-year-old Asian male presented with the symptoms of decreased vision and was found to have bilateral SRD involving fovea. There was no inflammation in the anterior chamber or vitreous. Physical examination showed hepatomegaly and splenomegaly. A blood count revealed white blood cell count of 38.2 × 109/L with 51.5% blast cells. Bone marrow aspirate showed total cell count of 145 × 103/µL with 80.6% blast cells and negative neutrophil myeloperoxidase staining. Cytogenetic analysis using fluorescence in situ hybridization confirmed a 9;22 chromosomal translocation, indicating the presence of the Philadelphia chromosome. Flow cytometry analysis demonstrated expression of CD10, CD19, and positive TdT. According to morphology, immunology, cytogenetics, and molecular criteria, the patient was diagnosed as having Philadelphia chromosome-positive lymphoid blast crisis of CML. Based on the ocular findings and hematological abnormalities, the SRD was considered to be ocular involvement secondary to the blast crisis of leukemia. Two months after starting induction therapy, fundus examination and optical coherence tomography showed complete resolution of bilateral SRD and improved vision. Prompt diagnosis of the disease leads to early systemic chemotherapy and may help restore visual function and improve survival.

Impact of low luminance conditions on quality of life for the visually impaired: development of the Low Luminance Questionnaire Japanese version.

PURPOSE: This study aimed to develop a Japanese version of the Low Luminance Questionnaire (LLQ-J) and to evaluate its reliability and validity. STUDY DESIGN: Cross-sectional study. METHODS: LLQ-J was developed by standardized methods. A total of 101 patients comprising 55 with age-related macular degeneration, 25 with glaucoma, 15 with regressed proliferative diabetic retinopathy, and 6 with retinitis pigmentosa were included in this study. The patients completed the LLQ-J and Japanese version of the visual function Questionnaire-25 (VFQ-25). Using the LLQ-J data, floor and ceiling effects were computed. To examine internal consistency, some patients completed the LLQ-J a second time 2-4 weeks later and the data were analyzed for Cronbach's alpha and intra-class correlation coefficients (ICCs). Best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) were measured, and low-luminance deficit (LLD) was calculated. Criterion validity was also tested. RESULTS: No ceiling or floor effects were present in the LLQ-J data. Cronbach's alfa was 0.88, and ICCs were higher than 0.70 for all subscales. Moderate to high correlation was observed between LLQ-J and VFQ-25 (p < 0.01), confirming concurrent validity. "General dim lighting" and "Peripheral vision" were significantly associated with LLVA in the better eye (p < 0.05). "Mobility", "General dim lighting" and "Peripheral vision" were significantly associated with LLD (p < 0.05). "Emotional distress" was significantly associated with BCVA in the worse eye (p < 0.05). No subscales were associated with BCVA of the better eye. CONCLUSIONS: The LLQ-J is a valid and reliable questionnaire for assessing QOL under low luminance conditions.

Syndecan-1 Promotes Streptococcus pneumoniae Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils.

Subversion of heparan sulfate proteoglycans (HSPGs) is thought to be a common virulence mechanism shared by many microbial pathogens. The prevailing assumption is that pathogens co-opt HSPGs as cell surface attachment receptors or as inhibitors of innate host defense. However, there are few data that clearly support this idea in vivo We found that deletion of syndecan-1 (Sdc1), a major cell surface HSPG of epithelial cells, causes a gain of function in a mouse model of scarified corneal infection, where Sdc1-/- corneas were significantly less susceptible to Streptococcus pneumoniae infection. Administration of excess Sdc1 ectodomains significantly inhibited S. pneumoniae corneal infection, suggesting that Sdc1 promotes infection as a cell surface attachment receptor. However, S. pneumoniae did not interact with Sdc1 and Sdc1 was shed upon S. pneumoniae infection, indicating that Sdc1 does not directly support S. pneumoniae adhesion. Instead, Sdc1 promoted S. pneumoniae adhesion by driving the assembly of fibronectin (FN) fibrils in the corneal basement membrane to which S. pneumoniae attaches when infecting injured corneas. S. pneumoniae specifically bound to corneal FN via PavA, and PavA deletion significantly attenuated S. pneumoniae virulence in the cornea. Excess Sdc1 ectodomains inhibited S. pneumoniae corneal infection by binding to the Hep II domain and interfering with S. pneumoniae PavA binding to FN. These findings reveal a previously unknown virulence mechanism of S. pneumoniae where key extracellular matrix (ECM) interactions and structures that are essential for host cell homeostasis are exploited for bacterial pathogenesis.IMPORTANCE Bacterial pathogens have evolved several ingenious mechanisms to subvert host cell biology for their pathogenesis. Bacterial attachment to the host ECM establishes a niche to grow and is considered one of the critical steps of infection. This pathogenic mechanism entails coordinated assembly of the ECM by the host to form the ECM structure and organization that are specifically recognized by bacteria for their adhesion. We serendipitously discovered that epithelial Sdc1 facilitates the assembly of FN fibrils in the corneal basement membrane and that this normal biological function of Sdc1 has detrimental consequences for the host in S. pneumoniae corneal infection. Our studies suggest that bacterial subversion of the host ECM is more complex than previously appreciated.

Unusual Case of Vogt-Koyanagi-Harada Disease Associated with SAPHO Syndrome: A Case Report.

A 66-year-old Japanese woman who was diagnosed with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome presented with bilateral blurred vision 4 months prior to visiting our hospital. She had visited a local ophthalmology clinic first. She was diagnosed with conjunctivitis and was prescribed antibacterial eye drops. The symptoms persisted in spite of treatment. She was then referred to our hospital. At her initial visit, the visual acuities were 0.6 in both eyes. A slit-lamp examination revealed bilateral shallow anterior chamber, and intraocular pressures of 18 mm Hg in the right eye and 16 mm Hg in the left eye. There were no cells in the anterior chamber. Fundus examination revealed bilateral annular choroidal detachment and serous retinal detachment. Fluorescein angiography showed leakage of dye from the retinal pigment epithelium (RPE) and indocyanine green angiography showed focal choroidal hypoperfusion. Optical coherence tomography showed wavy RPE line and blurry thick choroid. Systemic investigation by the physician demonstrated bilateral pleural effusions of unknown origin. The patient had a past history of breast cancer; however, no metastasis was identified via malignant cells through cytology, laboratory findings, radiographs, CT, and MRI. After the diagnosis of Vogt-Koyanagi-Harada (VKH) disease was made, the patient was treated with local and systemic steroid including high-dose intravenous corticosteroids, and 150 mg of cyclosporine per day. Seventy days after the second high-dose of intravenous corticosteroids, these medications brought a complete resolution of both choroidal and retinal detachment. VKH disease associated with SAPHO syndrome is rare. The combination of immunosuppressive drug and steroid might be helpful for severe cases of VKH disease.

Thymosin beta 4 is associated with RUNX2 expression through the Smad and Akt signaling pathways in mouse dental epithelial cells.

In previous studies by our group, we reported that thymosin beta 4 (Tb4) is closely associated with the initiation and development of the tooth germ, and can induce the expression of runt-related transcription factor 2 (RUNX2) during the development of the tooth germ. RUNX2 regulates the expression of odontogenesis-related genes, such as amelogenin, X-linked (Amelx), ameloblastin (Ambn) and enamelin (Enam), as well as the differentiation of osteoblasts during bone formation. However, the mechanisms through which Tb4 induces the expression of RUNX2 remain unknown. In the present study, we employed a mouse dental epithelial cell line, mDE6, with the aim to elucidate these mechanisms. The mDE6 cells expressed odontogenesis-related genes, such as Runx2, Amelx, Ambn and Enam, and formed calcified matrices upon the induction of calcification, thus showing characteristics of odontogenic epithelial cells. The expression of odontogenesis-related genes, and the calcification of the mDE6 cells were reduced by the inhibition of phosphorylated Smad1/5 (p-Smad1/5) and phosphorylated Akt (p-Akt) proteins. Furthermore, we used siRNA against Tb4 to determine whether RUNX2 expression and calcification are associated with Tb4 expression in the mDE6 cells. The protein expression of p-Smad1/5 and p-Akt in the mDE6 cells was reduced by treatment with Tb4-siRNA. These results suggest that Tb4 is associated with RUNX2 expression through the Smad and PI3K-Akt signaling pathways, and with calcification through RUNX2 expression in the mDE6 cells. This study provides putative information concerning the signaling pathway through which Tb4 induces RUNX2 expression, which may help to understand the regulation of tooth development and tooth regeneration.

Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma.

Recent studies have revealed that cancer cells are exacerbated by chronic inflammation. The present study examined the immunohistochemical expression for interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell carcinoma (OSCC) to elucidate the association of IL-6 expression with tumor progression, chemoresistance and prognosis. Seventy-eight patients with primary OSCC were analyzed by immunohistochemical staining for IL-6. These labeling indexes (LIs) were calculated and evaluated in association with the clinicopathologic characteristics and prognosis in the OSCC patients. The patients were divided into three groups as follows: negative group = LI <5%; low IL-6 group = 5% ≤ LI <30%; high IL-6 group = LI ≥30%. The patient numbers of the negative, low and high expression groups were 24, 22 and 32, respectively. In the high IL-6 expression group, IL-6 receptor (IL-6R), phosphor-signal tranducer and activator of transcription 3 (p-STAT3) were also detected in almost all the cancer cells. The prevalence of the cervical lymph node or the distant metastasis in the high expression group was significantly higher than those in the negative and low expression groups. Furthermore, the high expression group had a significantly poorer tumor response to the preoperative chemoradiotherapy and a more unfavourable prognosis than the negative and the low expression groups. Interestingly, IL-6, IL-6R and p-STAT3 were expressed in the residual cancer cells of all the patients in the high expression group with poor response to chemoradiotherapy. These results suggested that IL-6 signaling possibly is involved in the progression and treatment-resistance of OSCC and IL-6 expression in cancer cells could be a useful predictive factor of poor response to chemoradiotherapy and unfavorable prognosis.

Role of glycosaminoglycans in infectious disease.

Glycosaminoglycans (GAGs) have been shown to bind to a wide variety of microbial pathogens, including viruses, bacteria, parasites, and fungi in vitro. GAGs are thought to promote pathogenesis by facilitating pathogen attachment, invasion, or evasion of host defense mechanisms. However, the role of GAGs in infectious disease has not been extensively studied in vivo and therefore their pathophysiological significance and functions are largely unknown. Here we describe methods to directly investigate the role of GAGs in infections in vivo using mouse models of bacterial lung and corneal infection. The overall experimental strategy is to establish the importance and specificity of GAGs, define the essential structural features of GAGs, and identify a biological activity of GAGs that promotes pathogenesis.

[Mucoepidermoid carcinoma of the intrahepatic bile duct with metastasis to the cranial skin].

Mucoepidermoid carcinoma of the intrahepatic bile duct is a rare variant of cholangiocarcinoma: it is composed of mucus-secreting squamous cells and glandular cells within the same nests. This tumor is very aggressive, with high-grade malignancy, and has a poor prognosis. In the international literature, only 17 cases of mucoepidermoid carcinoma originating in the hepatic bile duct system have been reported until now. We report an autopsy case of mucoepidermoid carcinoma of the intrahepatic bile duct with metastasis to the cranial skin in a Japanese man who was more than 70 years old. This cancer metastasizes to many organs, but skin metastasis is extremely rare.

Increase in matrix metalloproteinase-2 level in the chicken retina after laser photocoagulation.

BACKGROUND AND OBJECTIVE: We investigated the levels of matrix metalloproteinase-2 (MMP-2), which has been implicated in various vitreoretinal diseases, in the retina after laser photocoagulation (LPC). MATERIALS AND METHODS: The time course of MMP-2 expression in 2-day-old chicken retinas before and 6 hours, 12 hours, 1 day, 2 days, 4 days, 8 days, 16 days, and 32 days after LPC was determined by real-time PCR and gelatin zymography. The basal level of MMP-2 in the retina and vitreous was also measured by gelatin zymography. MMP-2 localization in the retina was examined by immunohistochemistry. The localization of MMP-2 mRNA was determined by fluorescent in situ hybridization. The internal limiting membrane (ILM) was observed by scanning electron microscopy. RESULTS: MMP-2 mRNA expression in the retina peaked at day 4, but gelatin zymography showed that MMP-2 peaked 6 hours after LPC and the significant increase in the level of active MMP-2 lasted for more than 4 days. The concentration of MMP-2 in the vitreous was significantly higher than that in the retina. A distinct MMP-2 signal around the ILM was identified 6 hours after LPC, but MMP-2 mRNA was not detected there. Electron microscopy showed a damaged retinal surface after LPC. CONCLUSION AND OUTLOOK: The significant increase in retinal MMP-2 which lasted for more than 4 days after LPC may be induced by influx from the vitreous into the retina. This MMP-2 dynamics may contribute to pathological processes in the retina after LPC.

Distinct response to heparin by two chicken brain type creatine kinase subunits.

In the chicken, two creatine kinase-type B (B-CK) isoproteins, Ba- and Bb-CK, both of which are derived from a single copy gene by alternative splicing, dimerize in neural tissues. The two isoproteins contain distinct N-terminal portions, but their functional difference remains unknown. We investigated the binding affinities of Ba- and Bb-CK to heparin, hyaluronan and chondroitin sulfates, and examined the influence of these glycosaminoglycans on enzyme activity. Chicken retinal samples analyzed by Western blotting and amino acid sequence study after two-dimensional gel electrophoresis showed that heparin binds Bb-CK, but not Ba-CK, while hyaluronan and chondroitin sulfates showed no interaction with either isoprotein. Using fusion proteins covering the distinct N-terminal portions, we also showed that heparin did not react with the N-terminus of Ba-CK, but did react with that of Bb-CK. Site-directed mutagenesis of basic amino acids found in the N-terminal portion of Bb-CK identified three basic amino acids critical for this binding. Furthermore, heparin dose-dependently inhibited the enzymatic activities of Ba-CK; Bb-CK activities were less intensely inhibited. Hyaluronan and chondroitin sulfates had no effects on the activities of these enzymes. Thus, the N-terminal portion of B-CK is critical to mediate its affinity to heparin and control enzyme activity, which may be important for regulating energy metabolism in neural tissues such as brain and retina, unique organs abundant in heparan sulfates.

Competitive binding of heparin with hyaluronan to a specific motif in SPACR.

The critical hyaluronan binding motif (HABM) in sialoprotein associated with cones and rods (SPACR) has already been determined. As sialoproteoglycan associated with cones and rods, another interphotoreceptor matrix molecule, binds to chondroitin sulfate and heparin with or without the employment of HABMs, respectively, we evaluated and compared the binding of these glycosaminoglycans to SPACR. A western blotting study in combination with inhibition assays showed that heparin bound specifically to SPACR. A series of GST fusion proteins covering the whole SPACR molecule narrowed down the region responsible for the binding. Finally, a site-directed mutagenesis assay demonstrated that the critical HABM also acts as a specific binding site for heparin. These results were supported with mutual inhibitions by hyaluronan and heparin in analyses using GST fusion proteins and native SPACR derived from retina. Thus, these glycosaminoglycans bind to SPACR in a different manner than to sialoproteoglycan associated with cones and rods. The competitive binding between hyaluronan and heparin to SPACR, mediated through the identical HABM, may dominate the functions of SPACR, in turn involving physiological and pathological processes involved in retinal development, aging and other related disorders.

Characterization of a motif for specific binding to hyaluronan in chicken SPACR.

The chicken sialoprotein associated with cones and rods (SPACR) binds to hyaluronan (HA) in the interphotoreceptor matrix space, but the motif for HA binding is still unknown. This study was conducted to determine the critical site required for specific binding to HA. Western blotting study showed that SPACR binds biotinylated HA, and this interaction was specifically inhibited by unlabeled HA. A series of GST fusion proteins covering whole SPACR was prepared, and reactivity with HA was individually screened to narrow down the region for the binding. Further, putative HA-binding motif found near the carboxyl-terminus of SPACR was mutated by site-directed mutagenesis to identify the critical binding site. Finally, we showed that native SPACR derived from retina similarly binds to HA-affinity column under both reducing and non-reducing conditions. These results revealed that the specific putative HA-binding motif is located near the carboxyl-terminus of chicken SPACR, and suggested that a structural integrity such as folded structure is not largely involved in the HA binding.

Versican and fibrillin-1 form a major hyaluronan-binding complex in the ciliary body.

PURPOSE: In this study, biochemistry, molecular biology, immunohistochemistry, and electron microscopy techniques were used to examine whether versican, which is known to bind fibrillin-1, interacts with fibrillin-1 in the ciliary body and vitreous, and whether the versican in this complex binds to hyaluronan. METHODS: The new polyclonal antibodies against the amino and carboxyl termini of versican were raised and characterized. The mRNA expression levels of versican and fibrillin-1 were analyzed by RT-PCR and real-time PCR, and their protein levels were evaluated by Western blot analysis and immunohistochemistry. Isolation of versican bound to fibrillin-1-containing microfibrils from ciliary bodies was performed by extraction studies. Slot-blot analyses and rotary shadowing electron microscopy were applied to identify versican associated with fibrillin-1-containing microfibrils after gel filtration chromatography and density gradient centrifugation. RESULTS: The newly prepared polyclonal antibodies recognized amino and carboxyl termini of chicken versican. Versican, principally V0 and V1, was found to be securely bound to fibrillin-1-containing microfibrils, forming a major hyaluronan-binding structure in the ciliary nonpigmented epithelium. In addition, Western blot analysis revealed two cleaved complexes, the carboxyl-terminal end of versican bound to fibrillin microfibrils and the amino terminal end of versican bound to hyaluronan in the vitreous body. CONCLUSIONS: Fibrillin-1, versican, and hyaluronan form a unique complex in the ciliary nonpigmented epithelium, and two cleavage products of this complex were shown to exist in the vitreous body. This newly clarified fibrillin-versican-hyaluronan (FiVerHy) complex and its cleavage products may be indispensable for the physiological properties important to the ciliary body and vitreous.

[Marked effect of combination chemotherapy with tegafur-gimeracil-oteracil potassium and gemcitabine on a suspected case of pancreas cancer or gallbladder cancer metastasis to bone: further diagnosis of disseminated carcinomatosa of bone marrow recurrence after the 23 years of gastric cancer operation by autopsy findings].

A 70-year-old woman who underwent proximal gastrectomy for gastric cancer (poorly-differentiated adenocarcinoma) of Stage IIIB at age 46 visited our hospital April 2004 because of exacerbated pain by movement in the buttocks since November 2003. She showed multiple bone metastasis by CT (computerized tomography). Pancreas cancer or gallbladder cancer was suspected by CT, and a high tumor marker score (CA19-9 18,625 U/mL, DUPAN-II 15,000 U/ mL elevations were acknowledged). Although her symptoms were severe with performance status (PS) 4, she was administered combination chemotherapy with gemcitabine and cisplatin. After 2 cycle therapy, her PS was improved to 2, but the tumor markers had elevated. So we changed the chemotherapy menu to S-1 and gemcitabine. Her tumor markers lowered and PS was improved to 1. There was a remarkable response to this chemotherapy, and the result of CT and bone scintigraphy suggested that her bone metastasis was improved. Because of hematologic relapse due to DIC at 1 year after the first treatment, she was readmitted to our hospital and later died. The autopsical result revealed recurrence of gastric cancer 23 years post-operatively.

Cooling prevents induction of corneal damage by argon laser peripheral iridotomy.

PURPOSE: There are many reports of corneal complications caused by argon laser peripheral iridotomy. In this study, we investigated whether cooling the anterior ocular segment during laser iridotomy prevented corneal damage. METHODS: A space for cooling the anterior ocular segment by perfusion with ice-cold water was made between the cornea and a contact lens. Dutch pigmented rabbits were excessively irradiated by an argon green laser, aiming at the peripheral iris. We used a contact lens without a cooling system as a control. Temperature in the anterior chamber and intraocular pressure were also monitored throughout the experiment. RESULTS: During laser treatment, the temperature without the cooling system rose to a maximum of 44.5 degrees C in the anterior chamber, whereas use of the cooling system consistently kept this temperature at 11.1 degrees -16.1 degrees C. Although most eyes treated without cooling showed corneal damage, damage was seen in only a few or in no eyes cooled during laser treatment. CONCLUSIONS: Argon laser treatment using contact lenses with a cooling system drastically reduced the corneal damage induced by argon laser peripheral iridotomy. This technique may be acceptable for clinical use, considering its technical simplicity and low incidence of treatment-related complications.

Morphometric age-related evaluation of small retinal vessels by scanning laser Doppler flowmetry: determination of a vessel wall index.

BACKGROUND: Measurement of the retinal vessel wall thickness may contribute to the diagnosis of microvascular diseases. We present a methodical approach to calculate these alterations and to determine age-related differences. METHODS: One hundred fifty-three subjects without eye or internal diseases (mean age +/- SD, 47.6 +/- 14.9 years) underwent measurement of the retinal temporal superior artery and vein by scanning laser Doppler flowmetry (Heidelberg retina flowmeter). We calculated the difference between the diameter of reflectivity and the Doppler signal (Delta[VD-FD]/2) and determined a "vessel wall index" (VWI) by normalization of Delta(VD-FD)/2 for age and vessel diameter. RESULTS: Delta(VD-FD)/2 correlated with vessel diameter (artery, r = +0.60, P < 0.001; vein, r = +0.49, P<0.001) and age (artery, r = +0.19, P = 0.02; vein, r = +0.27, P = 0.001) but not with sex, if controlled for the other variables each. The venous, but not the arterial, vessel diameter correlated with age (r = +0.18, P = 0.02), if controlled for sex. The relative statistical weight of these empirical contributions to the variation observed in Delta(VD-FD)/2 was 36.5% (P < 0.001, artery) and 21.7% (P< 0.001, vein), and that of age was 3.6% (P = 0.02, artery) and 7.3% (P = 0.001, vein). The limit value of VWI to pathologic changes (80th percentile) was 1.25 microm/y (artery) and 1.31 microm/y (vein). Delta(VD-FD)/2 normalized for vessel diameter correlated with the 10-year categories of age (artery, r = +0.196, P = 0.017; vein, r = +0.250, P = 0.002). CONCLUSION: In a group of subjects aged 21 years to 70 years, we detected an increase of Delta(VD-FD)/2 in the retinal temporal superior artery and vein with age.

Molecular cloning and characterization of chick SPACRCAN.

MY-174, a monoclonal antibody that reacts with specific sialylated O-linked glycoconjugates of chick SPACR (sialoprotein associated with cones and rods), also recognizes another molecule of 300 kDa. Here, we verified that this 300-kDa molecule is chick SPACRCAN (sialoproteoglycan associated with cones and rods), another member of a novel interphotoreceptor matrix molecule family. Screening for chick SPACRCAN was carried out by plaque hybridization using a probe for chick SPACR. Specific polyclonal antibodies raised against chick SPACRCAN were used for the following experiments. To determine whether the 300-kDa molecule detected by MY-174 was identical to 300-kDa chick SPACRCAN, the migrations of these bands were examined after various glycosidase digestions. Furthermore, the expression levels were measured during retinal development and compared with those of chick SPACR. The results demonstrated that the 300-kDa molecule recognized by MY-174 was chick SPACRCAN, and we further identified it as a proteoglycan with chondroitin sulfate chains. SPACRCAN had heavily sialylated N- and O-linked glycoconjugates, and its MY-174 antigenicity was abolished by O-glycanase treatment after neuraminidase treatment, as observed for chick SPACR. During retinal development, the mRNA and core protein expression levels, MY-174 antigenicity, and hyaluronan binding ability of SPACRCAN peaked around embryonic day 17 and then gradually decreased, whereas the corresponding expression levels of SPACR simply increased, but not its hyaluronan binding ability. The MY-174 reactivity of SPACRCAN in the adult retina was decreased compared with that in the newborn retina, whereas that of SPACR was increased. The decreased hyaluronan binding of SPACR was induced by an inhibitory effect of the excess of sialic acids in the adult stage. Thus, with similar core protein structures and specific sialylated glycoconjugates but distinct chondroitin sulfate chains, SPACRCAN and SPACR may have separate roles in the retina due to their differing expression profiles during development.

Expression profile of heat shock protein 108 during retinal development in the chick.

In the developing chick retina, heat shock protein 108 (HSP108), which exhibits transferrin binding activity, has been demonstrated at the mRNA level, while transferrin shows two expression peaks. Here, we investigated the expression profile of HSP108 in the developing chick retina at the protein level. The localization of HSP108 in embryonic days 15 (E15), E18, and postnatal day 2 (P2) chick retina was examined immunohistochemically using monoclonal antibody 9G10 specific for chick HSP108, while the expression levels of HSP108 in developing chick retina from E12 to P2 and adult were measured by Western blot analysis. HSP108 was expressed in the ganglion cell layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner segments of photoreceptors and retinal pigment epithelium. Two peaks of HSP108 expression were found at around E13 and E18, respectively. Since the two HSP108 peaks appeared to be correlated with the transferrin expression peaks during retinal development, HSP108 may be associated with iron metabolism during the development of the retina.